tag:theconversation.com,2011:/us/topics/neurons-9368/articlesNeurons – The Conversation2024-02-29T19:06:47Ztag:theconversation.com,2011:article/2244942024-02-29T19:06:47Z2024-02-29T19:06:47ZWe discovered a ‘gentle touch’ molecule is essential for light tactile sensation in humans – and perhaps in individual cells<figure><img src="https://images.theconversation.com/files/578809/original/file-20240229-16-loeyq2.jpeg?ixlib=rb-1.1.0&rect=36%2C0%2C2692%2C2570&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/womans-hand-fern-leaf-man-nature-2190358695">Shutterstock</a></span></figcaption></figure><p>You were probably taught that we have five senses: sight, sound, smell, taste and touch. This is not quite right: “touch” is not a single sense, but rather several working together. </p>
<p>Our bodies contain a network of sensory nerve cells with endings sitting in the skin that detect an array of different physical signals from our environment. The pleasant sensation of a gentle touch feels distinct from the light pressure of our clothes or the hardness of a pencil gripped between our fingers, and all of these are quite different from the pain of a stubbed toe.</p>
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Read more:
<a href="https://theconversation.com/how-do-you-feel-your-sense-of-touch-is-several-different-senses-rolled-into-one-169344">How do you feel? Your 'sense of touch' is several different senses rolled into one</a>
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<p>How do these sensory neurons communicate such a wide range of different inputs? </p>
<p>In <a href="http://www.science.org/doi/10.1126/science.adl0495">new research published in Science</a>, the two co-authors of this article and our colleagues have found a force-sensing molecule in nerve cells called ELKIN1, which is specifically involved in detecting gentle touch. This molecule converts gentle touch into an electrical signal, the first step in the process of gentle touch perception.</p>
<h2>How we sense gentle touch</h2>
<p>Sensing gentle touch begins with tiny deformations of the skin due to a light brush. While they may not seem like much, these deformations generate enough force to activate sensory molecules that are found in specialised nerve endings in the skin. </p>
<p>These molecular force sensors form a pore in the surface of the cell that is closed until a force is applied. When the cell is indented, the pore opens and an electrical current flows. </p>
<p>This electrical current can generate a signal that moves along the sensory nerve to the spinal cord and up to the brain. </p>
<p>Our new research, led by Gary Lewin and Sampurna Chakrabarti from the Max Delbruck Center in Berlin, showed the force sensor ELKIN1 is necessary for us to detect very gentle touch.</p>
<p>They found mice lacking the ELKIN1 molecule did not appear to sense a cotton bud being gently drawn across their paw. The mice retained their ability to sense other environmental information, including other types of touch.</p>
<h2>Different molecules for different kinds of touch</h2>
<p>This new finding reveals one reason we can sense multiple types of “touch”: we have multiple, specialised force-sensing proteins that can help us distinguish different environmental signals. </p>
<p>ELKIN1 is the second touch-receptor molecule discovered in sensory neurons. The first (PIEZO2) was found in 2010 by Ardem Patapoutian, who was later awarded the Nobel Prize for the work. PIEZO2 is involved in sensing gentle touch, as well as a sense known as “proprioception”. Proprioception is the sense of where our limbs are in space that helps us regulate our movements.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A microscope image showing blobs of cyan, yellow and magenta." src="https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/578782/original/file-20240228-30-4t2s64.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Mouse neurons with the new ion channel ELKIN1 (cyan), which is responsible for touch sensation, nucleus (yellow) and the already known ion channel PIEZO2 (magenta).</span>
<span class="attribution"><span class="source">Sampurna Chakrabarti / Max Delbrück Center</span></span>
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<p>Identifying these force-sensing molecules is a challenge in itself. We need to be able to study nerve cells in isolation and measure electrical currents that flow into the cell while simultaneously applying controlled forces to the cells themselves. </p>
<h2>Do cells feel?</h2>
<p>While much of our research studied mouse neurons, not all scientific data obtained from mice can be directly translated to humans. </p>
<p>With team members at the University of Wollongong, one of us (Mirella Dottori) tried to determine whether ELKIN1 worked the same way in humans. They reprogrammed human stem cells to produce specialised nerve cells that respond to “touch” stimuli. In these human cells, ELKIN1 had similar functional properties of detecting touch. </p>
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<a href="https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A photo of a glass electrode prodding some cells in a Petri dish." src="https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/578781/original/file-20240228-24-4t2s64.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Experiments on sensory neurons confirmed the role of the ELKIN1 molecule.</span>
<span class="attribution"><span class="source">Felix Petermann / Max Delbrück Center</span></span>
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<p>While this research expands our understanding of how we make sense of the world around us, it also raises an additional, intriguing possibility. </p>
<p>ELKIN1 was first identified by one of us (Kate Poole) and her team at UNSW, with Gary Lewin and his team, while studying how melanoma cells break away from model tumours and “feel” their way through their surroundings. This could mean these tiny molecular force sensors give not only us, but our individual cells, a nuanced sense of touch.</p>
<p>Future research will continue to search for more molecular force sensors and endeavour to understand how they help our cells, and us, navigate our physical environment.</p><img src="https://counter.theconversation.com/content/224494/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kate Poole receives funding from the National Health and Medical Research Council, the Australian Research Council and the US Air Force Asian Office of Aerospace Research and Development
</span></em></p><p class="fine-print"><em><span>Mirella Dottori receives funding from the Australian Research Council, Medical Research Future Fund, Friedreich's Ataxia Research Alliance and Friedreich Ataxia Research Association. </span></em></p>Our bodies have a dedicated channel for sensing only the very lightest of touches.Kate Poole, Associate Professor in Physiology, UNSW SydneyMirella Dottori, Professor, University of WollongongLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2208282024-02-14T13:24:42Z2024-02-14T13:24:42ZWe designed wormlike, limbless robots that navigate obstacle courses − they could be used for search and rescue one day<figure><img src="https://images.theconversation.com/files/571646/original/file-20240126-17-1c52dw.JPG?ixlib=rb-1.1.0&rect=55%2C0%2C4024%2C1578&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Limbless robots may not need lots of complex algorithms when they have mechanical intelligence. </span> <span class="attribution"><span class="source">Tianyu Wang</span></span></figcaption></figure><p>Scientists have been trying to build <a href="https://en.wikipedia.org/wiki/Snakebot">snakelike, limbless robots</a> for decades. These robots could come in handy in <a href="https://www.science.org/content/article/searching-survivors-mexico-earthquake-snake-robots">search-and-rescue</a> situations, where they could navigate collapsed buildings to find and assist survivors. </p>
<p>With slender, flexible bodies, limbless robots could readily move through confined and cluttered spaces such as debris fields, where walking or wheeled robots and human rescuers tend to fail.</p>
<p>However, even the most advanced limbless robots have not come close to moving with the agility and versatility of worms and snakes in difficult terrain. Even the tiny nematode worm <em><a href="http://www.wormbook.org/">Caenorhabditis elegans</a></em>, which has a relatively simple nervous systems, can navigate through difficult physical environments. </p>
<p>As part of a team of <a href="https://www.lulab.gatech.edu/">engineers</a>, <a href="https://crablab.gatech.edu/">roboticists and physicists</a>, we wanted to explore this discrepancy in performance. But instead of looking to neuroscience for an answer, <a href="https://en.wikipedia.org/wiki/Biomechanics">we turned to biomechanics</a>. </p>
<p>We set out to build a robot model that drove its body using a mechanism similar to how worms and snakes power their movement. </p>
<h2>Undulators and mechanical intelligence</h2>
<p>Over thousands of years, organisms have evolved <a href="https://www.britannica.com/science/nervous-system">intricate nervous systems</a> that allow them to sense their physical surroundings, process this information and execute precise body movements to navigate around obstacles. </p>
<p>In robotics, engineers design algorithms that take in information from sensors on the robot’s body – a type of robotic nervous system – and use that information to decide how to move. These algorithms and systems are usually complex. </p>
<p>Our team wanted to figure out a way to simplify these systems by highlighting mechanically controlled approaches to dealing with obstacles that don’t require sensors or computation. To do that, we turned to examples from biology.</p>
<p>Animals don’t rely solely on their neurons – brain cells and <a href="https://my.clevelandclinic.org/health/body/23123-peripheral-nervous-system-pns">peripheral nerves</a> – to control movement. They also use the physical properties of their body – for example, the elasticity of their muscles – to help them react to their environment spontaneously, before their neurons even have a chance to respond.</p>
<p>While computational systems are governed by <a href="https://en.wikipedia.org/wiki/Computational_logic">the laws of mathematics</a>, mechanical systems are governed by physics. To achieve the same task, scientists can either design an algorithm or carefully design a physical system. </p>
<p>For example, limbless robots and animals move through the world by bending sections of their body left and right, <a href="https://en.wikipedia.org/wiki/Undulatory_locomotion">a type of movement called undulation</a>. If they collide with an obstacle, they have to turn away and go around it by bending more to one side than the other.</p>
<p>Scientists could achieve this with a robot by attaching sensors to its head or body. They could then design an algorithm that tells the robot to turn away or wind around the obstacle when it “feels” a large enough force on its head or body. </p>
<p>Alternatively, scientists could carefully select the robot’s materials and the arrangement and strength of its motors so that collisions would spontaneously produce a body shape that led to a turn. This robot would have what scientists call “mechanical intelligence.”</p>
<p>If scientists like us can understand how organisms’ bodies respond mechanically to contact with objects in their environment, we can design better robots that can deal with obstacles without having to program complex algorithms. </p>
<p>If you compare a diverse set of undulating organisms with the increasingly large zoo of <a href="https://en.wikipedia.org/wiki/Snakebot">robotic “snakes</a>,” one difference between the robots and biological undulators stands out. Nearly all undulatory robots bend their bodies using a series of connected segments with motors at each joint. But that’s not how living organisms bend.</p>
<p>In contrast, all limbless organisms, from large snakes to the lowly, microscopic nematode, achieve bends not from a single rotational joint-motor system but instead through <a href="http://www.wormbook.org/chapters/www_bodywallmuscle/bodywallmuscle.html">two bands of muscles</a> on either side of the body. To an engineer, this design seems counterintuitive. Why control something with two muscles or motors when one could do the job? </p>
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<a href="https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram showing a gray worm with a window showing the inside of the worm's body, which has two bands of muscle on the left and right side, cuticle on the top and nerve cord on the bottom, top and sides." src="https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=283&fit=crop&dpr=1 600w, https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=283&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=283&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=355&fit=crop&dpr=1 754w, https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=355&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/575078/original/file-20240212-26-it6ean.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=355&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Nematodes have two bands of muscle on the sides of their bodies that control motion.</span>
<span class="attribution"><span class="source">Ralf J. Sommer and WormAtlas</span></span>
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<p>To get to the bottom of this question, our team built a new robot called MILLR, for mechanically intelligent limbless robot, inspired by the two bands of muscle on snakes and worms. MILLR has two independently controlled cables that pull each joint left and right, bilaterally.</p>
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<a href="https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram showing the design of MILLR, with servo motors on each body segment, and cables and pulleys connecting them." src="https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=275&fit=crop&dpr=1 600w, https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=275&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=275&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=345&fit=crop&dpr=1 754w, https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=345&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/575079/original/file-20240212-20-gtf8t7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=345&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">MILLR’s design, inspired by nematode <em>C. elegans</em>.</span>
<span class="attribution"><span class="source">Tianyu Wang</span></span>
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<p><a href="https://doi.org/10.1126/scirobotics.adi2243">We found</a> this method allows the robot to spontaneously move around obstacles without having to sense its surroundings and actively change its body posture to comply to the environment.</p>
<h2>Building a mechanically intelligent robot</h2>
<p>Rather than mimicking the detailed muscular anatomy of a particular organism, MILLR applies forces to either side of the body by spooling and unspooling a cable. </p>
<p>This way, it mirrors the muscle activation methods that snakes and nematodes use, where the left and right sides take turns activating. This activation mode pulls the body toward one side or another by tightening on one side, while the other side relaxes and is pulled along passively. </p>
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<a href="https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="On the left, a photo showing a worm weaving between pegs. On the right, a photo showing a worm-like robot weaving between pegs." src="https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=122&fit=crop&dpr=1 600w, https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=122&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=122&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=153&fit=crop&dpr=1 754w, https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=153&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/575081/original/file-20240212-26-bro51v.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=153&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">MILLR’s design allows it to move through obstacles the same way worms do.</span>
<span class="attribution"><span class="source">Tianyu Wang and Christopher Pierce</span></span>
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</figure>
<p>By changing the amount of slack in the cables, <a href="https://doi.org/10.1126/scirobotics.adi2243">we can achieve</a> varying degrees of body stiffness. When the robot collides with an obstacle, depending on the cable tension, it selectively maintains its shape or bends under the force of the obstacle. </p>
<p><a href="https://doi.org/10.1126/scirobotics.adi2243">We found that</a> if the robot was actively bending to one side and it experienced a force in the same direction, the body complied to the force and bent further. If, alternatively, the robot experienced a force that opposed the bend, it would remain rigid and push itself off the obstacle. </p>
<p>Because of the pattern of the tension along the body, head-on collisions that would normally cause the robot to stop moving or jam itself instead naturally led to a redirection around the obstacle. The robot could push itself forward consistently. </p>
<h2>Testing MILLR</h2>
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<p>To investigate the benefits of mechanical intelligence, we built tiny obstacle courses and sent nematode worms through them to see how well they performed. We sent MILLR through a similar course and compared the results.</p>
<p>MILLR moved through its course <a href="https://doi.org/10.1126/scirobotics.adi2243">about as effectively as the real worms</a>. We noticed that the worms made the same type of body movements when they collided with obstacles as MILLR did.</p>
<p>The principles of mechanical intelligence could extend beyond the realm of nematodes. Future research could look at designing robots based on a host of other types of organisms for applications ranging from search and rescue to <a href="https://youtu.be/e0D9IVo-E9M?si=d8jGaC5GDLaMbEeS">exploring other planets</a>.</p><img src="https://counter.theconversation.com/content/220828/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This work was supported by the National Science Foundation Physics of Living Systems Student Research Network, NSF-Simons Southeast Center for Mathematics and Biology, Army Research Office Grant, and the Dunn Family Professorship.</span></em></p>Robots often have a hard time navigating through debris, but robots designed based on worms and snakes could move around obstacles faster, thanks to an idea called mechanical intelligence.Tianyu Wang, Ph.D. Student in Robotics, Georgia Institute of TechnologyChristopher Pierce, Postdoctoral Scholar in Physics, Georgia Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2169802023-12-21T21:37:49Z2023-12-21T21:37:49ZThe Douglas-Bell Canada Brain Bank: a goldmine for research on brain diseases<figure><img src="https://images.theconversation.com/files/557356/original/file-20231005-26-rmh9lm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4000%2C1508&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The experimental methods available today allow us to break the brain down into its elementary components in order to understand its functions and dysfunctions.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Human beings have always been fascinated by the brain. </p>
<p>Although scientific knowledge about this 1.3 kg of fragile substance embedded in our cranium has long been incomplete, dazzling technical breakthroughs made in recent years are now ushering in a Golden Age of molecular neuroscience. </p>
<p>These breakthroughs have been made possible partly thanks to brain banks, which preserve human brains in the best possible conditions for scientific research. Here in Montréal, we have one of the world’s largest such banks, the Douglas-Bell Canada Brain Bank (DBCBB), <a href="https://douglasbrainbank.ca">founded in 1980 at the Douglas Hospital</a>. </p>
<p>The DBCBB, which receives several brains each month, has collected over 3,600 specimens to date. Every year, its team processes dozens of tissue requests from scientists in Québec, Canada and abroad, preparing some 2,000 samples for research. </p>
<p>Over the past 40 years, these efforts have led to a considerable number of discoveries about different neurological and psychiatric diseases. </p>
<p>As a full professor in the department of psychiatry at McGill University, researcher at the Douglas Research Centre and director of the DBCBB since 2007, I work in close collaboration with <a href="https://www.mcgill.ca/psychiatry/gustavo-turecki">Dr. Gustavo Turecki</a>, co-director of the DBCBB and responsible for the component devoted to psychiatric illnesses and suicide.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&rect=14%2C2%2C1535%2C1231&q=45&auto=format&w=1000&fit=clip"><img alt="cerebral hemisphere" src="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&rect=14%2C2%2C1535%2C1231&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=475&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=475&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=475&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=596&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=596&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=596&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The Douglas-Bell Canada Brain Bank, which receives several brains each month, has collected over 3,600 specimens to date.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>A brief history of research on the human brain</h2>
<p>Scientists only began to identify the microscopic elements that make up the human brain in the second half of the 19th century. </p>
<p>That was when brains were preserved for the first time in formalin, a solution that preserves biological tissue so that it can be handled more easily and stored over a longer term.</p>
<p>At the same time, precision instruments and protocols were being developed that made it possible to examine the microscopic characteristics of nervous tissue.</p>
<p>Until the middle of the 20th century, researchers were mainly satisfied with preserving the brains of patients, taken during autopsies, so they could use them to identify possible macroscopic or microscopic changes linked to either neurological or psychiatric symptoms.</p>
<p>This is in fact what the German neurologist Alois Alzheimer did when he analyzed the brain of one of his patients suffering from dementia. In 1906, he described, for the first time, the microscopic lesions which characterize the disease that now bears his name.</p>
<p>Until the end of the 1970s, numerous collections of brain specimens preserved in formalin were built in hospital environments, a bit like the cabinets of curiosities of olden days.</p>
<p>Towards the end of the 20th century, new experimental approaches were developed allowing the high-resolution analysis of cells and molecules within biological tissues.</p>
<p>It then became necessary to collect and preserve human brains, obtained with the consent of the individual or his or her family, in conditions compatible with modern scientific techniques.</p>
<p>Researchers began freezing one of the cerebral hemispheres in order to measure its various molecular components. The other hemisphere was preserved in formalin to be used for macroscopic and microscopic anatomical studies.</p>
<p>This was the context in which the Douglas-Bell Canada Brain Bank was created.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The DBCBB premises" src="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Montréal is home to one of the world’s largest brain banks, the Douglas-Bell Canada Brain Bank, which was founded in 1980 at the Douglas Hospital.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>New experimental approaches are yielding results</h2>
<p>Leading researchers from many universities around the world now use DBCBB samples to advance their research. This, of course, includes a number of teams in Québec.</p>
<p>For example, with his team from the Douglas Research Centre, which is affiliated with McGill University, <a href="https://douglas.research.mcgill.ca/judes-poirier/">Judes Poirier</a> discovered that the APOE4 gene is a <a href="https://doi.org/10.1016/0140-6736(93)91705-Q">risk factor for Alzheimer’s disease</a>. More recently, the team of <a href="https://crhmr.ciusss-estmtl.gouv.qc.ca/en/researcher/gilbert-bernier">Gilbert Bernier</a>, professor in the department of neuroscience at Université de Montréal, discovered that the lesions characteristic of this disease are associated with <a href="https://doi.org/10.1038/s41598-018-37444-3">abnormal expression of the BMI1 gene</a>.</p>
<p>With regard to psychiatric illnesses, and more specifically depression, major progress has been made recently by the <a href="https://douglas.research.mcgill.ca/mcgill-group-suicide-studies-mgss/">McGill Group for Suicide Studies</a>. </p>
<p>Using cutting-edge methods to isolate and analyze human brain cells, Turecki’s team has succeeded in precisely identifying the cell types whose function is affected in men <a href="https://doi.org/10.1038/s41593-020-0621-y">who have suffered from major depression</a>, and then discovering that the cell types involved in this illness differ <a href="https://doi.org/10.1038/s41467-023-38530-5">between men and women</a>. </p>
<p>These experimental approaches generate huge data sets that can be examined in subsequent studies. This is the case, for example, of work carried out in my laboratory, which identified signs of persistent changes in neuroplasticity within the prefrontal cortex of people with a history of <a href="https://doi.org/10.1038/s41380-021-01372-y">child abuse</a>. In fact, the studies mentioned above enabled us to discover at least one of the cell types involved in this phenomenon. </p>
<p>In short, the experimental methods we have today allow us to break the brain down into its elementary components in order to understand its functions and dysfunctions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cerebral hemispheres preserved in formalin" src="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Leading researchers from many universities around the world benefit from Douglas-Bell Canada Brain Bank samples to advance their research.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>Identify, prevent, screen and treat</h2>
<p>Thanks to the hard work and dedication of the entire DBCBB team, as well as the unfailing support of all its partners, patrons (often anonymous) and funding bodies — particularly the FRQS research fund and Québec’s suicide research network, the <a href="https://reseausuicide.qc.ca">Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés</a> — this invaluable resource has not only managed to survive, but to grow and become one of the largest brain banks in the world. </p>
<p>There is every reason to believe that, in the years to come, the DBCBB will play an important role in the increasingly precise identification of the biological causes of brain diseases, and, as a result, will contribute to the identification of new targets for better approaches to prevention, screening and treatment.</p><img src="https://counter.theconversation.com/content/216980/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Naguib Mechawar has received funding from CIHR, NSERC, HBHL (CFREF) and FQRS (NEURON ERA-NET and RQSHA).</span></em></p>Montréal is home to one of the world’s largest brain banks, the Douglas-Bell Canada Brain Bank, where discoveries about different neurological and psychiatric diseases are made.Naguib Mechawar, Neurobiologiste, Institut Douglas; Professeur titulaire, Département de psychiatrie, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2200442023-12-18T16:17:12Z2023-12-18T16:17:12ZA new supercomputer aims to closely mimic the human brain — it could help unlock the secrets of the mind and advance AI<figure><img src="https://images.theconversation.com/files/566252/original/file-20231218-15-hajmbj.jpg?ixlib=rb-1.1.0&rect=19%2C9%2C6470%2C3940&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/businessman-touching-digital-human-brain-cell-582507070">Sdecoret / Shutterstock</a></span></figcaption></figure><p>A supercomputer scheduled to go online in April 2024 will rival the estimated rate of operations in the human brain, <a href="https://www.westernsydney.edu.au/newscentre/news_centre/more_news_stories/world_first_supercomputer_capable_of_brain-scale_simulation_being_built_at_western_sydney_university">according to researchers in Australia</a>. The machine, called DeepSouth, is capable of performing 228 trillion operations per second. </p>
<p>It’s the world’s first supercomputer capable of simulating networks of neurons and synapses (key biological structures that make up our nervous system) at the scale of the human brain.</p>
<p>DeepSouth belongs to an approach <a href="https://www.nature.com/articles/s43588-021-00184-y">known as neuromorphic computing</a>, which aims to mimic the biological processes of the human brain. It will be run from the International Centre for Neuromorphic Systems at Western Sydney University.</p>
<p>Our brain is the most amazing computing machine we know. By distributing its
computing power to billions of small units (neurons) that interact through trillions of connections (synapses), the brain can rival the most powerful supercomputers in the world, while requiring only the same power used by a fridge lamp bulb.</p>
<p>Supercomputers, meanwhile, generally take up lots of space and need large amounts of electrical power to run. The world’s most powerful supercomputer, the <a href="https://www.hpe.com/uk/en/compute/hpc/cray/oak-ridge-national-laboratory.html">Hewlett Packard Enterprise Frontier</a>, can perform just over one quintillion operations per second. It covers 680 square metres (7,300 sq ft) and requires 22.7 megawatts (MW) to run. </p>
<p>Our brains can perform the same number of operations per second with just 20 watts of power, while weighing just 1.3kg-1.4kg. Among other things, neuromorphic computing aims to unlock the secrets of this amazing efficiency.</p>
<h2>Transistors at the limits</h2>
<p>On June 30 1945, the mathematician and physicist <a href="https://www.ias.edu/von-neumann">John von Neumann</a> described the design of a new machine, the <a href="https://ieeexplore.ieee.org/document/194089">Electronic Discrete Variable Automatic Computer (Edvac)</a>. This effectively defined the modern electronic computer as we know it. </p>
<p>My smartphone, the laptop I am using to write this article and the most powerful supercomputer in the world all share the same fundamental structure introduced by von Neumann almost 80 years ago. <a href="https://www.sciencedirect.com/topics/computer-science/von-neumann-architecture">These all have distinct processing and memory units</a>, where data and instructions are stored in the memory and computed by a processor.</p>
<p>For decades, the number of transistors on a microchip doubled approximately every two years, <a href="https://ieeexplore.ieee.org/abstract/document/591665">an observation known as Moore’s Law</a>. This allowed us to have smaller and cheaper computers. </p>
<p>However, transistor sizes are now approaching the atomic scale. At these tiny sizes, excessive heat generation is a problem, as is a phenomenon called quantum tunnelling, which interferes with the functioning of the transistors. <a href="https://qz.com/852770/theres-a-limit-to-how-small-we-can-make-transistors-but-the-solution-is-photonic-chips#:%7E:text=They're%20made%20of%20silicon,we%20can%20make%20a%20transistor.">This is slowing down</a> and will eventually halt transistor miniaturisation.</p>
<p>To overcome this issue, scientists are exploring new approaches to
computing, starting from the powerful computer we all have hidden in our heads, the human brain. Our brains do not work according to John von Neumann’s model of the computer. They don’t have separate computing and memory areas. </p>
<p>They instead work by connecting billions of nerve cells that communicate information in the form of electrical impulses. Information can be passed from <a href="https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials-and-synapses">one neuron to the next through a junction called a synapse</a>. The organisation of neurons and synapses in the brain is flexible, scalable and efficient. </p>
<p>So in the brain – and unlike in a computer – memory and computation are governed by the same neurons and synapses. Since the late 1980s, scientists have been studying this model with the intention of importing it to computing.</p>
<figure class="align-center ">
<img alt="Microchip." src="https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/566265/original/file-20231218-25-yjbwxy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The continuing miniaturisation of transistors on microchips is limited by the laws of physics.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-presentation-new-generation-microchip-gloved-691548583">Gorodenkoff / Shutterstock</a></span>
</figcaption>
</figure>
<h2>Imitation of life</h2>
<p>Neuromorphic computers are based on intricate networks of simple, elementary processors (which act like the brain’s neurons and synapses). The main advantage of this is that these machines <a href="https://www.electronicsworld.co.uk/advances-in-parallel-processing-with-neuromorphic-analogue-chip-implementations/34337/">are inherently “parallel”</a>. </p>
<p>This means that, <a href="https://www.pnas.org/doi/full/10.1073/pnas.95.3.933">as with neurons and synapses</a>, virtually all the processors in a computer can potentially be operating simultaneously, communicating in tandem.</p>
<p>In addition, because the computations performed by individual neurons and synapses are very simple compared with traditional computers, the energy consumption is orders of magnitude smaller. Although neurons are sometimes thought of as processing units, and synapses as memory units, they contribute to both processing and storage. In other words, data is already located where the computation requires it.</p>
<p>This speeds up the brain’s computing in general because there is no separation between memory and processor, which in classical (von Neumann) machines causes a slowdown. But it also avoids the need to perform a specific task of accessing data from a main memory component, as happens in conventional computing systems and consumes a considerable amount of energy. </p>
<p>The principles we have just described are the main inspiration for DeepSouth. This is not the only neuromorphic system currently active. It is worth mentioning the <a href="https://www.humanbrainproject.eu">Human Brain Project (HBP)</a>, funded under an <a href="https://ec.europa.eu/futurium/en/content/fet-flagships.html">EU initiative</a>. The HBP was operational from 2013 to 2023, and led to BrainScaleS, a machine located in Heidelberg, in Germany, that emulates the way that neurons and synapses work. </p>
<p><a href="https://www.humanbrainproject.eu/en/science-development/focus-areas/neuromorphic-computing/hardware/">BrainScaleS</a> can simulate the way that neurons “spike”, the way that an electrical impulse travels along a neuron in our brains. This would make BrainScaleS an ideal candidate to investigate the mechanics of cognitive processes and, in future, mechanisms underlying serious neurological and neurodegenerative diseases.</p>
<p>Because they are engineered to mimic actual brains, neuromorphic computers could be the beginning of a turning point. Offering sustainable and affordable computing power and allowing researchers to evaluate models of neurological systems, they are an ideal platform for a range of applications. They have the potential to both advance our understanding of the brain and offer new approaches to artificial intelligence.</p><img src="https://counter.theconversation.com/content/220044/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Domenico Vicinanza does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Neuromorphic computers aim to one day replicate the amazing efficiency of the brain.Domenico Vicinanza, Associate Professor of Intelligent Systems and Data Science, Anglia Ruskin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2153262023-10-13T18:04:37Z2023-10-13T18:04:37ZAn itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin<figure><img src="https://images.theconversation.com/files/553357/original/file-20231011-23-fpzuw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2168%2C1381&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Itching, and the subsequent urge to scratch, can make eczema worse.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/scratching-chest-royalty-free-image/1463546524">Kinga Krzeminska/Moment via Getty Images</a></span></figcaption></figure><p>Itching can be uncomfortable, but it’s a normal part of your skin’s immune response to external threats. When you’re itching from an encounter with poison ivy or mosquitoes, consider that your urge to scratch may have evolved to get you to <a href="https://doi.org/10.1083/jcb.201603042">swat away disease-carrying pests</a>. </p>
<p>However, for many people who suffer from chronic skin diseases like eczema, the sensation of itch can <a href="https://eczema.org/information-and-advice/living-with-eczema/itching-and-scratching/">fuel a vicious cycle</a> of scratching that interrupts sleep, reduces productivity and <a href="https://nationaleczema.org/eczema-emotional-wellness/">prevents them from enjoying daily life</a>. This cycle is caused by <a href="https://nationaleczema.org/blog/why-does-eczema-itch/#">sensory neurons and skin immune cells</a> working together to promote itching and skin inflammation.</p>
<p>But, paradoxically, some of the mechanisms behind this feedback loop also stop inflammation from getting worse. In our newly published research, my team of immunologists and neuroscientists <a href="https://profiles.ucsf.edu/marlys.fassett">and I</a> discovered that a specific type of itch-sensing neuron can <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">push back on the itch-scratch-inflammation cycle</a> in the presence of a small protein. This protein, called <a href="https://doi.org/10.1016/j.jaci.2013.10.048">interleukin-31, or IL-31</a>, is typically involved in triggering itching. </p>
<p>This negative feedback loop – like the vicious cycle – is only possible because the itch-sensing nerve endings in your skin are closely intertwined with the millions of cells that <a href="https://doi.org/10.4049/jimmunol.1801473">make up your skin’s immune system</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/_VhcZTGv0CU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Your skin has its own immune system.</span></figcaption>
</figure>
<h2>IL-31: An itchy molecule</h2>
<p>The protein IL-31 is key to the connection between the nervous and immune systems. This molecule is <a href="https://doi.org/10.1038/ni1084">produced by some immune cells</a>, and like other <a href="https://my.clevelandclinic.org/health/body/24585-cytokines">members of this molecule family</a>, it specializes in helping immune cells communicate with each other. </p>
<p>IL-31 is rarely present in the skin or blood of people who don’t have a history of eczema, allergies, asthma or related conditions. But those with conditions like eczema that cause chronic itch have significantly <a href="https://doi.org/10.3389/fmed.2021.638325">increased skin production of IL-31</a>. There is strong evidence that IL-31 is one of a small set of proteins that immune cells produce that can bind directly to sensory neurons and <a href="https://doi.org/10.1016/j.cell.2013.08.057">trigger itching</a>. Small amounts of purified IL-31 injected directly into skin or spinal fluid leads to impressively <a href="https://doi.org/10.1016/j.jaci.2013.10.048">rapid-onset itching and scratching</a>.</p>
<p>However, when my colleagues and I induced rashes in mice by exposing them to dust mites, we found that itch-sensing neurons turned down the dial on inflammation at the site of itching instead of promoting it. They did so by secreting <a href="https://doi.org/10.1007/978-1-61779-310-3_1">small molecules called neuropeptides</a> that, in this context, directed immune cells to respond less enthusiastically. In sum, we had discovered an inverse relationship between itching and skin inflammation, tethered by a single molecule.</p>
<p>But if IL-31 triggers itching, which can worsen inflammation by making patients scratch their skin, how does it reduce inflammation? </p>
<p>We found the answer to this paradox in a little-known function of sensory neurons called <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurogenic-inflammation">neurogenic inflammation</a>. This nerve reflex triggers sensory neurons to release various signaling molecules directly into tissues, including <a href="https://doi.org/10.1111/1523-1747.ep12455620">specific neuropeptides that promote signs of inflammation</a> like increased blood flow to the skin. Neurogenic inflammation acts within the same nerves that transmit sensory information like itch, pain, touch and temperature, but differs by the path it takes: away from the brain rather than toward it.</p>
<p>We discovered that IL-31 can induce neurogenic inflammation, <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">mapping a direct pathway</a> going from IL-31 through sensory neurons to repress immune cells in the skin. When we engineered mice to be unresponsive to IL-31, we similarly found that they had more activated skin immune cells that produced more inflammation. This means the net effect of IL-31 is to blunt overall inflammation.</p>
<h2>IL-31 as potential treatment</h2>
<p>Our study shows that IL-31 causes sensory neurons in the skin to perform <a href="https://www.science.org/doi/10.1126/sciimmunol.abi6887">two very different functions</a>: They signal inward to the spinal cord and brain to stimulate an itching sensation that typically leads to more inflammation, but they also signal back out to the skin and quell inflammation by inhibiting certain immune cells.</p>
<p>Although paradoxical, this makes evolutionary sense. Scratching an itch can feel very satisfying but doesn’t have much utility in the modern world where we’re more likely to suffer from compulsive scratching than encounter stinging nettles. In contrast, unchecked inflammation underlies many chronic autoimmune diseases. Therefore, turning off an immune response in inflamed tissue can be as important as turning it on.</p>
<p>Our discoveries raise important questions about the implications of modifying IL-31 to treat different diseases. For one, it isn’t clear how IL-31-sensing neurons interface with <a href="https://doi.org/10.1038/s41590-019-0493-z">other neuronal circuits</a> that also regulate skin inflammation. Furthermore, some patients have <a href="https://doi.org/10.1056/NEJMoa1606490">higher levels of allergic proteins</a> in their blood or <a href="https://doi.org/10.1111/jdv.17218">develop asthma flares</a> when taking existing drugs that target IL-31. IL-31 is also found in some lung and gut cells – how and why would an itch-inducing molecule be present in internal organs? </p>
<p>Anatomical niches where sensory neurons and immune cells converge are present throughout the human body. If an itchy molecule like IL-31 can use neuronal circuitry to dampen an immune response in the skin, similar molecules like those used in <a href="https://migrainetrust.org/live-with-migraine/healthcare/treatments/gepants/">migraine drugs</a> could be repurposed to treat skin conditions, too.</p><img src="https://counter.theconversation.com/content/215326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marlys Fassett receives funding from the National Institutes of Health/National Institute of Arthritis, Musculoskeletal and Skin Diseases. She also serves as a grant reviewer for the National Eczema Association.</span></em></p>Itch-sensing neurons in your skin are intertwined with your immune cells. Counterintuitively, the molecule that connects them triggers responses that both worsen and improve skin conditions.Marlys Fassett, Associate Professor of Dermatology, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2044422023-10-02T12:27:51Z2023-10-02T12:27:51ZPsychedelics plus psychotherapy can trigger rapid changes in the brain − new research at the level of neurons is untangling how<figure><img src="https://images.theconversation.com/files/549891/original/file-20230924-22-cjkf2k.jpg?ixlib=rb-1.1.0&rect=1516%2C67%2C5741%2C3842&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New research hints at how psychedelics can trigger rapid, lasting change.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/psychedelic-drug-royalty-free-image/1306005226">wildpixel/iStock via Getty Images Plus</a></span></figcaption></figure><p>The <a href="https://www.verywellmind.com/what-is-brain-plasticity-2794886">human brain can change</a> – but usually only slowly and with great effort, such as when learning a new sport or foreign language, or recovering from a stroke. Learning new skills <a href="https://doi.org/10.1056/NEJMcibr1100496">correlates with changes in the brain</a>, as evidenced by neuroscience <a href="https://theconversation.com/cognitive-flexibility-is-essential-to-navigating-a-changing-world-new-research-in-mice-shows-how-your-brain-learns-new-rules-204259">research with animals</a> and functional brain scans in people. Presumably, if you master Calculus 1, something is now different in your brain. Furthermore, <a href="https://doi.org/10.1152/japplphysiol.00515.2006">motor neurons in the brain expand and contract</a> depending on how often they are exercised – a neuronal reflection of “use it or lose it.”</p>
<p>People may wish their brains could change faster – not just when learning new skills, but also when overcoming problems like anxiety, depression and addictions.</p>
<p>Clinicians and scientists know there are times the brain can make rapid, enduring changes. Most often, these <a href="https://doi.org/10.1016/S0079-6123(07)67012-5">occur in the context of traumatic experiences</a>, leaving an indelible imprint on the brain.</p>
<p>But positive experiences, which alter one’s life for the better, can occur equally as fast. Think of a <a href="https://doi.org/10.3389/fpsyg.2021.720579">spiritual awakening</a>, a <a href="https://doi.org/10.1177/0022167819892107">near-death experience</a> or a <a href="https://doi.org/10.1037/emo0000442">feeling of awe in nature</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a road splits in the woods, sun shines through green leafy trees" src="https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/549892/original/file-20230924-29-mhzjw2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A transformative experience can be like a fork in the road, changing the path you are on.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/germany-bavaria-franconia-spessart-track-in-forest-royalty-free-image/634474863">Westend61 via Getty Images</a></span>
</figcaption>
</figure>
<p>Social scientists call events like these psychologically transformative experiences or <a href="https://doi.org/10.1177/0269881120959637">pivotal mental states</a>. For the rest of us, they’re forks in the road. Presumably, <a href="https://doi.org/10.1002/9781118591277.ch18">these positive experiences</a> quickly change some “wiring” in the brain. </p>
<p>How do these rapid, positive transformations happen? It seems the brain has a way to facilitate accelerated change. And here’s where it gets really interesting: Psychedelic-assisted psychotherapy appears to tap into this natural neural mechanism.</p>
<h2>Psychedelic-assisted psychotherapy</h2>
<p>Those who’ve had a psychedelic experience usually describe it as a mental journey that’s impossible to put into words. However, it can be conceptualized as an <a href="https://en.wikipedia.org/wiki/Psychedelic_experience">altered state of consciousness</a> with distortions of perception, modified sense of self and rapidly changing emotions. Presumably there is a relaxation of the higher brain control, which allows deeper brain thoughts and feelings to emerge into conscious awareness.</p>
<p><a href="https://theconversation.com/psychedelic-medicine-is-on-its-way-but-its-not-doing-shrooms-with-your-shrink-heres-what-you-need-to-know-208568">Psychedelic-assisted psychotherapy</a> combines the <a href="https://theconversation.com/medication-can-help-you-make-the-most-of-therapy-a-psychologist-and-neuroscientist-explains-how-209200">psychology of talk therapy</a> with the power of a psychedelic experience. <a href="https://doi.org/10.1056/NEJMp2300936">Researchers have described cases</a> in which subjects report profound, personally transformative experiences after one six-hour session with the psychedelic substance psilocybin, taken in conjunction with psychotherapy. For example, <a href="https://nyulangone.org/news/single-dose-hallucinogenic-drug-psilocybin-relieves-anxiety-depression-patients-advanced-cancer">patients distressed about advancing cancer</a> have quickly experienced relief and an unexpected acceptance of the approaching end. How does this happen?</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="glowing green tendrils of a neuron against a black background" src="https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548902/original/file-20230918-27-lsrzu2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Neuronal spines are the little bumps along the spreading branches of a neuron.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Dendriticspines.jpg">Patrick Pla via Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Research suggests that <a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">new skills, memories</a> and attitudes are encoded in the brain by new connections between neurons – sort of like branches of trees growing toward each other. Neuroscientists even call the pattern of growth <a href="https://dictionary.apa.org/arborization">arborization</a>. </p>
<p>Researchers using a technique called <a href="https://doi.org/10.1038/nmeth818">two-photon microscopy</a> can observe this process in living cells by following the formation and regression of spines on the neurons. The spines are one half of the synapses that allow for communication between one neuron and another.</p>
<p>Scientists have thought that enduring spine formation could be established only with focused, repetitive mental energy. However, a lab at Yale recently documented <a href="https://doi.org/10.1016/j.neuron.2021.06.008">rapid spine formation in the frontal cortex of mice</a> after one dose of psilocybin. Researchers found that mice given the mushroom-derived drug had about a 10% increase in spine formation. These changes had occurred when examined one day after treatment and endured for over a month.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of little bumps along a neuron, enlarged at different scales" src="https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=267&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=267&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=267&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=335&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=335&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551075/original/file-20230928-21-8ym7k7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=335&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tiny spines along a neuron’s branches are a crucial part of how one neuron receives a message from another.</span>
<span class="attribution"><span class="source">Edmund S. Higgins</span></span>
</figcaption>
</figure>
<h2>A mechanism for psychedelic-induced change</h2>
<p>Psychoactive molecules primarily change brain function through the receptors on the neural cells. The serotonin receptor 5HT, the one famously <a href="https://doi.org/10.1186/s13041-017-0306-y">tweaked by antidepressants</a>, comes in a variety of subtypes. Psychedelics such as DMT, the active chemical in the plant-based psychedelic <a href="https://www.britannica.com/science/ayahuasca">ayahuasca</a>, <a href="https://doi.org/10.1126/science.adf0435">stimulate a receptor cell type</a>, called 5-HT2A. This receptor also <a href="https://doi.org/10.1017/S0954579417001274">appears to mediate the hyperplastic states</a> when a brain is changing quickly.</p>
<p>These 5-HT2A receptors that DMT activates are not only on the neuron cell surface but also inside the neuron. It’s only the 5-HT2A receptor inside the cell that facilitates rapid change in neuronal structure. <a href="https://doi.org/10.1126/science.adg2989">Serotonin can’t get through the cell membrane</a>, which is why people don’t hallucinate when taking antidepressants like Prozac or Zoloft. The psychedelics, on the other hand, slip through the cell’s exterior and tweak the 5-HT2A receptor, stimulating dendritic growth and increased spine formation.</p>
<p>Here’s where this story all comes together. In addition to being the active ingredient in ayahuasca, <a href="https://doi.org/10.1038/s41598-019-45812-w">DMT is an endogenous molecule</a> synthesized naturally in mammalian brains. As such, human neurons are capable of producing their own “psychedelic” molecule, although likely in tiny quantities. It’s possible the brain uses its own endogenous DMT as a tool for change – as when forming dendritic spines on neurons – to encode pivotal mental states. And it’s possible psychedelic-assisted psychotherapy uses this naturally occurring neural mechanism to facilitate healing.</p>
<h2>A word of caution</h2>
<p>In her essay collection “<a href="https://www.harpercollins.com/products/these-precious-days-ann-patchett?variant=40104586641442">These Precious Days</a>,” author Ann Patchett describes taking mushrooms with a friend who was <a href="https://theconversation.com/psychedelics-may-better-treat-depression-and-anxiety-symptoms-than-prescription-antidepressants-for-patients-with-advanced-cancer-201937">struggling with pancreatic cancer</a>. The friend had a mystical experience and came away feeling deeper connections to her family and friends. Patchett, on the other hand, said she spent eight hours “hacking up snakes in some pitch-black cauldron of lava at the center of the Earth.” It felt like death to her. </p>
<p>Psychedelics are powerful, and none of the classic psychedelic drugs, such as LSD, are approved yet for treatment. The U.S. Food and Drug Administration in 2019 did <a href="https://theconversation.com/fda-approves-promising-new-drug-called-esketamine-for-treatment-resistant-depression-111966">approve ketamine</a>, in conjunction with an antidepressant, to treat depression in adults. Psychedelic-assisted psychotherapy <a href="https://doi.org/10.1038/s41591-021-01336-3">with MDMA (often called ecstasy or molly) for PTSD</a> and <a href="https://doi.org/10.1056/NEJMoa2206443">psilocybin for depression</a> are in Phase 3 trials.</p><img src="https://counter.theconversation.com/content/204442/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Higgins is an unpaid member of the safety board for the Multidisciplinary Association for Psychedelic Studies (MAPA) for their phase 3 trials with MDMA for PTSD.</span></em></p>Change in the brain usually comes with plenty of effort over time. Neuroscientists are working to understand how psychedelic drugs provide a shortcut that seems to rely on existing brain systems.Edmund S. Higgins, Affiliate Associate Professor of Psychiatry & Family Medicine, Medical University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2119852023-09-18T12:19:28Z2023-09-18T12:19:28ZDopamine is a brain chemical famously linked to mood and pleasure − but researchers have found multiple types of dopamine neurons with different functions<figure><img src="https://images.theconversation.com/files/548136/original/file-20230913-15-lb61w.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A better understanding of dopamine could lead to better treatments for neurodegenerative and neurodevelopmental diseases, among others.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/dopaminergic-neuron-illustration-royalty-free-illustration/956352542">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Dopamine seems to be having a moment in the zeitgeist. You may have read about it <a href="https://www.nytimes.com/2023/06/30/well/mind/dopamine-brain-behavior.html">in the news</a>, seen <a href="https://www.cosmopolitan.com/uk/body/a41799984/low-dopamine-morning-routine-tiktok-hack/">viral social media posts</a> about “dopamine hacking” or <a href="https://hubermanlab.com/controlling-your-dopamine-for-motivation-focus-and-satisfaction/">listened to podcasts</a> about how to harness what this molecule is doing in your brain to improve your mood and productivity. But recent neuroscience research suggests that popular strategies to control dopamine are based on an overly narrow view of how it functions.</p>
<p>Dopamine is one of the <a href="https://nida.nih.gov/research-topics/parents-educators/lesson-plans/mind-matters/drugs-and-brain">brain’s neurotransmitters</a> – tiny molecules that act as messengers between neurons. It is known for its role in tracking your reaction to rewards such as food, sex, money or answering a question correctly. There are many <a href="http://dx.doi.org/10.1016/j.celrep.2014.10.008">kinds of</a> <a href="https://doi.org/10.1038/s41593-018-0203-4">dopamine neurons</a> located in the uppermost region of the brainstem that manufacture and release dopamine throughout the brain. Whether neuron type affects the function of the dopamine it produces has been an open question.</p>
<p>Recently published research reports a relationship between neuron type and dopamine function, and one type of dopamine neuron has an <a href="https://doi.org/10.1038/s41593-023-01401-9">unexpected function</a> that will likely reshape how scientists, clinicians and the public understand this neurotransmitter.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/OYGp9JHPrTU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Dopamine is involved with more than just pleasure.</span></figcaption>
</figure>
<h2>Dopamine neuron firing</h2>
<p>Dopamine is famous for the role it plays in reward processing, an idea that dates back <a href="https://doi.org/10.1017/S0033291700045232">at least 50 years</a>. Dopamine neurons monitor the difference between the rewards you thought you would get from a behavior and what you actually got. Neuroscientists call this difference a <a href="https://doi.org/10.1523/JNEUROSCI.16-05-01936.1996">reward prediction error</a>.</p>
<p>Eating dinner at a restaurant that just opened and looks likely to be nothing special shows reward prediction errors in action. If your meal is very good, that results in a positive reward prediction error, and you are likely to return and order the same meal in the future. Each time you return, the reward prediction error shrinks until it eventually reaches zero when you fully expect a delicious dinner. But if your first meal was terrible, that results in a negative reward prediction error, and you probably won’t go back to the restaurant.</p>
<p>Dopamine neurons communicate reward prediction errors to the brain through their firing rates and patterns of dopamine release, which the brain <a href="https://doi.org/10.1038/nature05051">uses for learning</a>. They <a href="https://doi.org/10.1146/annurev-neuro-110920-011929">fire in two ways</a>. </p>
<p>Phasic firing refers to rapid bursts that cause a short-term peak in dopamine. This happens when you receive an unexpected reward or more rewards than anticipated, like if your server offers you a free dessert or includes a nice note and smiley face on your check. Phasic firing encodes reward prediction errors.</p>
<p>By contrast, tonic firing describes the slow and steady activity of these neurons when there are no surprises; it is background activity interspersed with phasic bursts. Phasic firing is like mountain peaks, and tonic firing is the valley floors between peaks.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting the phasic peaks and tonic valleys of dopamine levels" src="https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=775&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=775&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=775&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=974&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=974&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548148/original/file-20230913-34250-qasdbb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=974&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows the phasic peaks and tonic valleys of dopamine levels, the former encoding unexpected rewards and the latter encoding expected events.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1523/JNEUROSCI.1894-10.2010">Dreyer et al. 2010/Journal of Neuroscience</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<h2>Dopamine functions</h2>
<p>Tracking information used in generating reward prediction errors is not all dopamine does. I have been following all the other jobs of dopamine <a href="https://scholar.google.com/citations?user=z3XmbfYAAAAJ&hl=en">with interest</a> <a href="https://doi.org/10.3758/s13415-013-0191-5">through</a> <a href="https://doi.org/10.1523/JNEUROSCI.0927-14.2015">my own</a> <a href="https://doi.org/10.1016/j.bpsc.2021.05.002">research measuring</a> brain areas where dopamine neurons are located in people.</p>
<p>About 15 years ago, reports started coming out that dopamine neurons <a href="https://doi.org/10.1073/pnas.0811507106">respond to</a> <a href="https://doi.org/10.1038/nature08028">aversive events</a> – think brief discomforts like a puff of air against your eye, a mild electric shock or losing money – something scientists thought dopamine <a href="https://doi.org/10.1126/science.1093360">did not do</a>. These studies showed that some dopamine neurons respond only to rewards while others respond to both rewards and negative experiences, leading to the hypothesis that there might be <a href="https://doi.org/10.1016/j.neuron.2010.11.022">more than one dopamine system</a> in the brain.</p>
<p>These studies were soon followed by experiments showing that there is more than one type of dopamine neuron. So far, researchers have identified <a href="https://doi.org/10.1016/j.tins.2020.01.004">seven distinct types</a> of dopamine neurons by looking at their genetic profiles.</p>
<p>A study published in August 2023 was the first to parse <a href="https://doi.org/10.1038/s41593-023-01401-9">dopamine function based on neuron subtype</a>. The researchers at the <a href="http://www.dombecklab.org">Dombeck Lab</a> at Northwestern University examined three types of dopamine neurons and found that two tracked rewards and aversive events while the third monitored movement, such as when the mice they studied started running faster.</p>
<h2>Dopamine release</h2>
<p>Recent media coverage on how to control dopamine’s effects is based only on the type of release that looks like peaks and valleys. When dopamine neurons fire in phasic bursts, as they do to signal reward prediction errors, dopamine is released throughout the brain. These <a href="https://doi.org/10.1146/annurev.neuro.28.061604.135722">dopamine peaks happen very fast</a> because dopamine neurons can fire many times in less than a second.</p>
<p>There is another way that dopamine release happens: Sometimes it increases slowly until a desired reward is obtained. Researchers discovered this <a href="https://doi.org/10.1038/nature12475">ramp pattern</a> 10 years ago in a part of the brain called the striatum. The steepness of the dopamine ramp tracks how valuable a reward is and how much effort it takes to get it. In other words, it encodes motivation. </p>
<p>The restaurant example can also illustrate what happens when dopamine release occurs in a ramping pattern. When you have ordered a meal you know is going to be amazing and are waiting for it to arrive, your dopamine levels are steadily increasing. They reach a crescendo when the server places the dish on your table and you sink your teeth into the first bite.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of ramp pattern dopamine release, which shows a steep rise that levels off" src="https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=287&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=287&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=287&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=360&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=360&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548573/original/file-20230915-17-1ivozh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=360&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram shows a ramp pattern dopamine release, reaching a peak when a reward is obtained.</span>
<span class="attribution"><a class="source" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751524/">Collins et al. 2016/Scientific Reports</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>How dopamine ramps happen is still unsettled, but this type of release is thought to underlie <a href="https://doi.org/10.1146/annurev-psych-010814-015044">goal pursuit and learning</a>. Future research on dopamine ramping will affect how scientists understand motivation and will ultimately improve advice on how to optimally hack dopamine.</p>
<h2>Dopamine(s) in disease and neurodiversity</h2>
<p>Though dopamine is known for its involvement in <a href="https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/drugs-brain">drug addiction</a>, <a href="https://www.nia.nih.gov/health/parkinsons-disease">neurodegenerative disease</a> and <a href="https://theconversation.com/misuse-of-adderall-promotes-stigma-and-mistrust-for-patients-who-need-it-a-neuroscientist-explains-the-science-behind-the-controversial-adhd-drug-198223">neurodevelopmental conditions</a> like attention-deficit/hyperactivity disorder, recent research suggests how scientists understand its involvement may soon need updating. Of the seven subtypes of dopamine neurons that are known so far, researchers have characterized the function of only three. </p>
<p>There is already some evidence that the discovery of dopamine diversity is updating scientific knowledge of disease. The researchers of the recent paper identifying the relationship between dopamine neuron type and function point out that <a href="https://doi.org/10.1038/s41593-023-01401-9">movement-focused dopamine neurons</a> are known to be among the hardest hit in Parkinson’s disease, while two other types are not as affected. This difference might lead to more targeted treatment options.</p>
<p>Ongoing research untangling the diversity of dopamine will likely continue to change, and improve, our understanding of disease and neurodiversity.</p><img src="https://counter.theconversation.com/content/211985/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kimberlee D'Ardenne currently receives funding from the National Institutes of Health (R21-MH130924-01) and has received other funding from the National Institutes of Health and the National Science Foundation in the past. She is also a member of the National Association of Science Writers and of the Board of Editors in the Life Sciences.</span></em></p>From dopamine hacking to dopamine detoxes, some people have sought to harness this brain chemical to improve their mood and productivity. But it’s far more complicated than that.Kimberlee D'Ardenne, Assistant Research Professor in Psychology, Arizona State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2116852023-08-17T13:16:40Z2023-08-17T13:16:40ZHow consciousness may rely on brain cells acting collectively – new psychedelics research on rats<figure><img src="https://images.theconversation.com/files/542999/original/file-20230816-31-hyq6mq.jpg?ixlib=rb-1.1.0&rect=123%2C113%2C3470%2C2581&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics can help uncover consciousness. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/will-universe-remember-me-series-artistic-484612375">agsandrew/Shutterstock</a></span></figcaption></figure><p>Psychedelics are known for inducing <a href="https://theconversation.com/how-lsd-helped-us-probe-what-the-sense-of-self-looks-like-in-the-brain-57703">altered states of consciousness</a> in humans by fundamentally changing our normal pattern of sensory perception, thought and emotion. Research into the therapeutic potential of psychedelics <a href="https://theconversation.com/psychedelics-how-they-act-on-the-brain-to-relieve-depression-183320">has increased significantly</a> in the last decade. </p>
<p>While this research is important, I have always been more intrigued by the idea that psychedelics can be used as a tool to study the neural basis of human consciousness in laboratory animals. We ultimately share the same basic neural hardware with other mammals, and possibly some basic aspects of consciousness, too. So by examining what happens in the brain when there’s a psychedelically induced change in conscious experience, we can perhaps glean insights into what consciousness is in the first place.</p>
<p>We still don’t know a lot about how the networks of cells in the brain enable conscious experience. The dominating view is that consciousness somehow emerges as a collective phenomenon when the dispersed information processing of individual neurons (brain cells) is integrated as the cells interact.</p>
<p>But the mechanism by which this is supposed to happen remains unclear. Now our <a href="https://www.nature.com/articles/s42003-023-05093-6">study on rats</a>, published in Communications Biology, suggests that psychedelics radically change the way that neurons interact and behave collectively.</p>
<p>Our study compared two different classes of psychedelics in rats: the classic LSD type and the less-typical ketamine type (ketamine is an anaesthetic in larger doses). Both classes are known to induce psychedelic experiences in humans, despite acting on different receptors in the brain. </p>
<h2>Exploring brain waves</h2>
<p>We used electrodes to simultaneously measure electrical activity from 128 separate areas of the brain of nine awake rats while they were given psychedelics. The electrodes could pick up two kinds of signals: <a href="https://www.scientificamerican.com/article/what-is-the-function-of-t-1997-12-22/">electrical brain waves</a> caused by the cumulative activity in thousands of neurons, and smaller transient electrical pulses, called action potentials, from individual neurons.</p>
<p>The classic psychedelics, such as LSD and psilocybin (the active ingredient in magic mushrooms), activates a receptor in the brain (5-HT2A) which normally binds to <a href="https://my.clevelandclinic.org/health/articles/22572-serotonin#:%7E:text=Serotonin%20is%20a%20chemical%20that,blood%20clotting%20and%20sexual%20desire.">serotonin</a>, a neurotransmitter that regulates mood and many other things. Ketamine, on the other hand, works by inhibiting another receptor (NMDA), which normally is activated by <a href="https://my.clevelandclinic.org/health/articles/22839-glutamate">glutamate</a>, the primary neurotransmitter in the brain for making neurons fire. </p>
<p>We speculated that, despite these differences, the two classes of psychedelics might have similar effects on the activity of brain cells. Indeed, it turned out that both drug classes induced a very similar and distinctive pattern of brain waves in multiple brain regions. </p>
<p>The brain waves were unusually fast, oscillating about 150 times per second. They were also surprisingly synchronised between different brain regions. Short bursts of oscillations at a similar frequency are known to occur occasionally under normal conditions in some brain regions. But in this case, it occurred for prolonged durations.</p>
<figure class="align-center ">
<img alt="Brain waves on electroencephalogram EEG." src="https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=337&fit=crop&dpr=1 600w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=337&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=337&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=423&fit=crop&dpr=1 754w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=423&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/543191/original/file-20230817-19-49zwoq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=423&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Brain waves on electroencephalogram EEG.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/brain-wave-on-electroencephalogram-eeg-epilepsy-575882314">Chaikom/Shutterstock</a></span>
</figcaption>
</figure>
<p>First, we assumed that a single brain structure was generating the wave and that it then spread to other locations. But the data was not consistent with that scenario. Instead, we saw that the waves went up and down almost simultaneously in all parts of the brain where we could detect them – a phenomenon called <a href="https://www.nature.com/articles/35067550#:%7E:text=Phase%20synchronization%20refers%20to%20the,signals%20regardless%20of%20signal%20amplitude.">phase synchronisation</a>. Such tight phase synchronisation over such long distances has to our knowledge never been observed before.</p>
<p>We were also able to measure action potentials from individual neurons during the psychedelic state. Action potentials are electrical pulses, no longer than a thousandth of a second, that are generated by the opening and closing of ion channels in the cell membrane. The action potentials are the primary way that neurons influence each other. Consequently, they are considered to be the main carrier of information in the brain.</p>
<p>However, the action potential activity caused by LSD and ketamine differed significantly. As such, they could not be directly linked to the general psychedelic state. For LSD, neurons were inhibited – meaning they fired fewer action potentials – in all parts of the brain. For ketamine, the effect depended on cell type – certain large neurons were inhibited, while a type of smaller, locally connecting neurons, fired more. </p>
<p>Therefore, it is probably the synchronised wave phenomenon – how the neurons behave collectively – that is most strongly linked to the psychedelic state. Mechanistically, this makes some sense. It is likely that this type of increased synchrony has large effects on the integration of information across neural systems that normal perception and cognition rely on.</p>
<p>I think that this possible link between neuron-level system dynamics and consciousness is fascinating. It suggests that consciousness relies on a coupled collective state rather than the activity of individual neurons – it is greater than the sum of its parts.</p>
<p>That said, this link is still highly speculative at this point. That’s because the phenomenon has not yet been observed in human brains. Also, one should be cautious when extrapolating human experiences to other animals – it is of course impossible to know exactly what aspects of a trip we share with our rodent relatives. </p>
<p>But when it comes to cracking the deep mystery of consciousness, every bit of information is valuable.</p><img src="https://counter.theconversation.com/content/211685/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Pär Halje receives funding from The Crafoord Foundation, Royal Physiographic Society of Lund, Magnus Bergvall Foundation, Olle Engkvist Foundation, The Swedish Parkinson Foundation, Petrus and Augusta Hedlund Foundation, Thorsten and Elsa Segerfalk Foundation, The Swedish Society for Medical Research (SSMF), Fredrik and Ingrid Thuring Foundation and Åhlén Foundation.</span></em></p>We still don’t know a lot about how the networks of cells in the brain enable conscious experience.Pär Halje, Associate Research Fellow of Neurophysiology, Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2086392023-07-04T15:11:39Z2023-07-04T15:11:39ZBiting flies are attracted to blue traps – we used AI to work out why<p>Flies which feast on blood – such as tsetse and horse flies – inflict painful bites and spread debilitating diseases among people and animals alike. So a lot of work has gone into designing the most efficient traps to control the populations of these flies.</p>
<p>Biting fly traps tend to be blue, because decades of field research has shown that such flies find this colour especially attractive. But it’s never been clear why these flies find blue to be so irresistible – especially since blue objects are not a common sight in the natural environment.</p>
<p>Scientists have speculated that blue surfaces might look like <a href="https://royalsocietypublishing.org/doi/10.1098/rsbl.2003.0121">shaded places</a> to flies since shadows have a blueish tinge. Tsetse flies in particular seek out such shaded spots to rest in, which might explain their attraction to blue traps. </p>
<p>Another possibility is that blue surfaces might <a href="https://resjournals.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2915.1999.00163.x">lure hungry flies</a> by providing them with the telltale signs they use to distinguish animals against a background of foliage. According to this theory, a fly might mistake a blue trap for an animal it wishes to bite and feed upon. </p>
<figure class="align-left ">
<img alt="A blue canvas, diamond shaped container is suspended from a tree." src="https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535007/original/file-20230630-24873-ovj9iw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A bright blue trap for tsetse flies is suspended from a tree.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bright-blue-trap-dangerous-tsetse-fly-724357057">Fabian Plock/Shutterstock</a></span>
</figcaption>
</figure>
<p>But assessing these possibilities is especially tricky because flies perceive colour differently to people. Humans perceive colour using the responses of three kinds of light-detecting photoreceptor in the retina which are broadly sensitive to blue, green and red wavelengths of light.</p>
<p>But most “higher flies” – such as tsetse and horseflies – have five kinds of photoreceptor sensitive to UV, blue and green wavelengths. So, a blue trap won’t look the same to a fly as it does to the human who designed it.</p>
<h2>From flies to AI…</h2>
<p>In <a href="https://royalsocietypublishing.org/doi/10.1098/rspb.2023.0463#d1e1574">our study</a>, we tackled the problem by using artificial intelligence (AI). We used artificial neural networks which are a form of machine learning inspired by the structure of real nervous systems. Artificial neural networks learn by modifying the strengths of connections between a network of artificial neurons.</p>
<p>We fed these networks with the photoreceptor signals that a fly would experience when looking at animals or foliage backgrounds, both in light and in shade. We then trained the networks to distinguish animals from leaves, and shaded from unshaded objects, using only that visual information.</p>
<p>The trained networks would find the most efficient way of processing the visual signals, which we expected to share properties with the mechanisms that have evolved in real flies’ nervous systems. We then investigated whether the artificial neural networks classified blue traps as animals or as shaded surfaces.</p>
<h2>Blueness or brightness?</h2>
<p>After training, our neural networks could easily distinguish animals from leaf backgrounds, and shaded from unshaded stimuli, using the sensory information available to a fly. However, what surprised us was that they solved these problems in completely different ways.</p>
<p>The networks identified shade using brightness and not colour – quite simply, the darker a stimulus appeared, the more likely it was to be classified as shaded. Meanwhile, animals were identified using the relative strength of blue and green photoreceptor signals. Relatively greater blue compared to green signals indicated that a stimulus was probably an animal rather than a leaf, and vice versa.</p>
<p>The implications of this became clear when we fed these networks the visual signals caused by blue traps. The blue traps were never mistaken for shaded surfaces, but they were commonly misclassified as animals.</p>
<figure class="align-center ">
<img alt="A close up of an insect with huge blue/green eyes" src="https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535038/original/file-20230630-13700-zuvny9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The horse fly (<em>Hybomitra epistates</em>) can inflict painful bites upon people and livestock.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/horse-fly-hybomitra-epistates-portrait-1773555527">Mircea Costina/Shutterstock</a></span>
</figcaption>
</figure>
<p>Of course, artificial neural networks are not real flies, nor exact models of a fly’s nervous system. But they do show us the most efficient way of processing a fly’s visual signals to identify natural stimuli. And we expect evolution to have taken advantage of similar principles in real fly nervous systems.</p>
<p>The best way to identify shade using the visual information a fly has is through brightness and not blueness. Meanwhile, the best way of identifying animals was, somewhat counterintuitively, using blueness. Such a mechanism is very strongly stimulated by blue traps, explaining why they prove such a powerful lure for hungry flies. Further evidence for this idea comes from field studies which show that tsetse landing on coloured traps are <a href="https://resjournals.onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-3032.1990.tb00519.x">relatively starved</a>.</p>
<p>If we can understand the sensory signals and behaviour that cause flies to be caught in traps, we can engineer traps to more efficiently exploit those mechanisms and more effectively control the flies. We’ve already had <a href="https://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0007905#:%7E:text=Tsetse%20can%20be%20controlled%20using%20insecticide-treated%20fabric%20targets%2C,these%20fabrics%20to%20be%20more%20attractive%20to%20tsetse.">some success</a> in doing this for tsetse flies.</p>
<p>More effective traps will help minimise the impacts of those flies on health and welfare of people and animals. They could help prevent the damaging effects of biting flies on livestock, help in the fight against dangerous fly-borne diseases such as <a href="https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness)">sleeping sickness</a>, and protect us and animals from fly attacks in general.</p><img src="https://counter.theconversation.com/content/208639/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Roger Santer has received funding from the Knowledge Economy Skills Scholarships program, and from the Centre for International Development Research at Aberystwyth (CIDRA). </span></em></p>New research on what attracts blood-feasting flies to blue objects could help minimise the impacts of those insects on people and animals.Roger Santer, Lecturer in Zoology, Aberystwyth UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2072832023-06-13T18:25:16Z2023-06-13T18:25:16ZSeeing dead fruit flies is bad for the health of fruit flies – and neuroscientists have identified the exact brain cells responsible<figure><img src="https://images.theconversation.com/files/531186/original/file-20230609-5996-byp5nm.png?ixlib=rb-1.1.0&rect=0%2C0%2C2510%2C1995&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">For _Drosophila melanogaster_, their senses have a significant effect on how quickly they age.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/drosophila-melanogaster-royalty-free-image/108149276">nico_blue/E+ via Getty Images</a></span></figcaption></figure><p><a href="https://www.ncbi.nlm.nih.gov/books/NBK10041/">All living organisms age</a>. People have long sought ways to slow, halt or reverse this process, which is commonly associated with declining mental and physical health. One area researchers are probing is the role that sensory perception – such as sight, smell, sound, taste and touch – plays on health and life span. </p>
<p>While you may typically think of your senses as what you use to gather information about your surroundings, recent work has demonstrated that environmental cues themselves can <a href="https://doi.org/10.1016/j.tem.2016.03.007">affect physiology and aging</a>. Your body regulates itself to match the conditions it finds itself in. The <a href="https://doi.org/10.1146/annurev-physiol-021119-034440">nervous system is poised as a central player</a> in mediating the effects of sensory perception. It stores and integrates incoming information from the environment and interprets and disseminates information across different tissues. </p>
<p>I have used fruit flies, specifically <em>Drosophila melanogaster</em>, for more than 15 years to better understand how <a href="https://www.researchgate.net/profile/Christi-Gendron">sensory perception affects aging</a>. Recently my work has focused on the role the brain plays in aging, looking at how death perception, or when fruit flies perceive other dead fruit flies, affects their life span. My colleagues and I have shown that when fruit flies see, and to a lesser extent smell, an excess of dead flies in their environment, they <a href="https://doi.org/10.1038/s41467-019-10285-y">avoid other flies and undergo significant physiological changes</a>, including rapid decreases in stored fat, decreased resistence to starvation and shortened life span. While it is currently unknown whether these changes are evolutionarily advantageous, we speculate that it could be, because of the stressful environment that the living flies find themselves in.</p>
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<figcaption><span class="caption">Fruit flies are among the most common model organisms in research.</span></figcaption>
</figure>
<p>In our newly published research, my colleagues and I identified the <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002149">neural circuits and signaling processes</a> behind the physiological effects, including rapid aging, that occur when <em>Drosophila</em> encounter their dead. Because other animals also experience physiological effects in the presence of their dead, identifying how this process works in fruit flies could shed light on how it operates in other species, including in people.</p>
<h2>Neuroscience of death perception</h2>
<p>Using genetic tools that detect which neurons are likely activated when live flies are exposed to dead flies, we identified a handful of neurons in the <em>Drosophila</em> brain called R2/R4 neurons that <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002149">act as a rheostat for aging</a>. These neurons are the center of sensory information processing and motor coordination in fruit fly brains. Inhibiting or activating them changed the aging rate of the flies, suggesting that these neurons alter fly life span in response to perceiving dead flies.</p>
<p>Next, we wanted to identify which molecules produced by R2/R4 neurons were responsible for spurring aging after flies witnessed other dead flies. Since components of a signaling pathway involved in glucose regulation have <a href="https://doi.org/10.1038/nature08980">long been associated with aging</a>, we focused on a protein called Foxo that is associated with the pathway.</p>
<p>We discovered that flies without Foxo had similar life spans whether or not there were dead flies present. We saw the same result when we decreased the amount of Foxo in R2/R4 neurons. These findings suggest that <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002149">Foxo in R2/R4 neurons</a> plays a key role in changing the life span of living flies.</p>
<p>We also discovered that other components of the signaling pathway involved in glucose regulation, called <a href="http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002149"><em>Drosophila</em> insulin-like peptides, or dilps</a>, mediate the effect of death perception on life span. Because these molecules appeared after changes in R2/R4 neuron activity, this suggests that they do not directly affect Foxo in these neurons. They likely work on other tissues.</p>
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<figcaption><span class="caption">Ring neurons like R2/R4 are involved in fruit fly sensory processing and motor coordination.</span></figcaption>
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<h2>Evolution of sensory perception effects on aging</h2>
<p>There are many examples of how sensory perception affects aging in animals, suggesting that it is a phenomenon that occurs across species. </p>
<p>For example, manipulating specific subsets of sensory neurons in the worm <a href="https://doi.org/10.1016/s0896-6273(03)00816-x"><em>Caenorhabditis elegans</em></a> can either shorten or extend its life span. Genetically manipulating fruit flies to <a href="https://doi.org/10.1126/science.1136610">lose their sense of smell</a> makes them live longer. Furthermore, environmental cues that indicate the presence of <a href="https://doi.org/10.1093/gerona/glv039">food</a>, <a href="https://doi.org/10.1073/pnas.1315461111">water</a>, <a href="https://doi.org/10.1371/journal.pbio.1000356">danger</a> and <a href="https://doi.org/10.1126/science.1243339">potential mates</a> all significantly influence physiology and longevity. </p>
<p>Manipulating the sensory system can affect aging even in mammals. For example, <a href="https://doi.org/10.1016/j.cell.2014.03.051">losing a specific pain receptor</a> can significantly extend the life span of mice.</p>
<p>The effects of seeing dead fruit flies on the physiology of fruit flies resemble changes seen in other species. For instance, <a href="https://doi.org/10.1073/pnas.0901270106">social insects</a> like ants and honeybees carry their dead away from the colony in a behavior called necrophoresis. <a href="https://doi.org/10.1098/rspb.2005.3378">Nonhuman primates</a> also experience increased glucocorticoid levels when a relative dies. This suggests that the processes that mediate these changes have similarities across species. My research team has previously shown that the effects of death perception in <em>Drosophila</em> involved chemical compounds and neural signaling that have been <a href="https://doi.org/10.1038/s41467-019-10285-y">conserved throughout evolution</a>.</p>
<p>The specific cues that lead to changes in the life spans of worms, flies and mice are likely species-specific. But the fact that they are all affected by changes in sensory input suggests that the molecular mechanisms driving age-related changes may be shared by all, including people.</p>
<p>Altogether, our work provides insight into the neural underpinnings of how the senses affect aging. While translating these findings to humans is clearly speculative, we hope that more research can eventually help researchers better understand the physiological and psychological effects of people who routinely witness death, such as soldiers and first responders.</p><img src="https://counter.theconversation.com/content/207283/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christi Gendron does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>When fruit flies see other dead fruit flies, their life spans are cut short. Other species also undergo analogous physiological changes when seeing their dead.Christi Gendron, Research Assistant Professor of Molecular and Integrative Physiology, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2013892023-06-11T20:52:50Z2023-06-11T20:52:50ZWhat’s a TENS machine? Can it help my period pain or endometriosis?<figure><img src="https://images.theconversation.com/files/529235/original/file-20230531-17-nf3bmd.jpg?ixlib=rb-1.1.0&rect=1%2C0%2C997%2C667&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cropped-close-view-girl-touch-stomach-1354368302">Shutterstock</a></span></figcaption></figure><p>If you’ve been on social media recently you might have noticed sponsored posts and ads for a variety of small, portable electrical devices. These claim to manage period or <a href="https://www.endometriosisaustralia.org/about-endo">endometriosis</a> pain safely and without drugs.</p>
<p>Most devices have a small box that generates an electrical pulse, and wires connected to sticky pads, which go on your tummy.</p>
<p>So how are these devices supposed to stop your pain? Are they safe? Do they actually work?</p>
<p><div data-react-class="InstagramEmbed" data-react-props="{"url":"https://www.instagram.com/p/CT7o8DnPaXs","accessToken":"127105130696839|b4b75090c9688d81dfd245afe6052f20"}"></div></p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/health-check-are-painful-periods-normal-62290">Health Check: are painful periods normal?</a>
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</em>
</p>
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<h2>They’re mini TENS machines</h2>
<p>These devices use “transcutaneous electrical nerve stimulation”, better known as TENS. In other words, they apply small electrical pulses across the skin to stimulate certain types of nerves.</p>
<p>TENS machines are not new. They’ve been around since the <a href="https://patents.google.com/patent/US3817254">1970s</a> and have been used for a <a href="https://www.healthdirect.gov.au/tens">variety of painful conditions</a>, from muscular injuries to pain relief in labour. </p>
<p>However, these latest devices are compact and easy to wear discretely compared to the older models. They’re fairly simple to use, portable, you can use them at home, and they cost around A$50-200. </p>
<p>It’s easy to see why devices like these might be popular. <a href="https://doi.org/10.1016/j.jpag.2020.11.007">Half</a> of people with period pain say over-the-counter medication such as ibuprofen doesn’t get rid of their period pain. Most people with endometriosis <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/imj.15494">report</a> major issues with getting adequate pain relief.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-sharp-butt-pains-to-period-poos-5-lesser-known-menstrual-cycle-symptoms-191352">From sharp butt pains to period poos: 5 lesser-known menstrual cycle symptoms</a>
</strong>
</em>
</p>
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<h2>How might TENS work?</h2>
<p>All TENS-based devices generate small electrical pulses that feel a little like <a href="https://patient.info/treatment-medication/painkillers/tens-machines">mild electrical shocks</a>. These pulses are transmitted through the surface of the skin via the sticky pads. </p>
<p>You generally place these pads where the pain is. So for period pain that’s usually at or below the level of the belly button but above the pubic region. You can also place the pads on your lower back or even on your tailbone (sacrum). This is because some nerves near your tailbone also affect the pelvic area.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Sticky pad of TENS machine on skin" src="https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529236/original/file-20230531-21-4m3nnt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">You place two sticky pads on your tummy or lower back.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/tens-electrodes-positioned-back-pain-treatment-466080803">Shutterstock</a></span>
</figcaption>
</figure>
<h2>Here’s what we know so far</h2>
<p>The exact mechanisms of how TENS works to reduce pain is still unclear. There are likely <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011890.pub3/full">many different pathways</a>. </p>
<p>First, we need to first talk about different types of nerves. <a href="https://www.ncbi.nlm.nih.gov/books/NBK10965/">Nociceptors</a> are nerves that send “danger” impulses about actual or potential tissue damage. Sensory nerves in your skin transmit information about things such as touch and pressure.</p>
<p>The <a href="https://www.science.org/doi/10.1126/science.150.3699.971">gate control theory of pain</a> says the spinal cord has “gates” that can be open or closed. When these gates are open, nerves can transmit these danger impulses up the spinal cord to the brain where they may be interpreted as “pain”. If these gates are closed, these impulses can’t reach the brain as easily.</p>
<p>TENS machines, especially at high frequency (greater than 50 pulses per second), tend to stimulate <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011890.pub3/full">sensory nerves</a> (the ones in your skin). These sensory nerves also send signals to your brain, but faster than the danger ones.</p>
<p>These sensory signals can close the “gates” at certain parts of the spinal cord. So if the TENS machine can stimulate enough of these sensory nerves in your skin, it will block at least some of these danger impulses from reaching the brain. The fewer danger impulses that reach the brain, the less pain you are likely to feel.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Closed farm gate across dirt track" src="https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529241/original/file-20230531-27-4m3nnt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">TENS machines may close the ‘gates’ at certain parts of the spinal cord so fewer ‘danger’ impulses reach the brain.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-iron-farm-field-gate-red-2260337685">Shutterstock</a></span>
</figcaption>
</figure>
<p>Then there’s the concept of <a href="https://www.news-medical.net/health/What-are-Endogenous-Opioids.aspx">endogenous opioids</a> as pain relief. These are pain relieving chemicals the body makes itself. </p>
<p>TENS machines stimulate the release of these chemicals, with different types of endogenous opioids released depending on the frequency of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027071/">stimulation</a>. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-pain-and-what-is-happening-when-we-feel-it-49040">Explainer: what is pain and what is happening when we feel it?</a>
</strong>
</em>
</p>
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<h2>So does TENS work?</h2>
<p><strong>For period pain</strong></p>
<p>A systematic <a href="https://www.sciencedirect.com/science/article/pii/S155083072030286X">review</a> in 2022 found four studies looking at TENS to manage primary dysmenorrhea (period pain that occurs without any physical changes in the pelvis).</p>
<p>There was a significant reduction in period pain when high-frequency TENS (more than 50 pulses per second) was compared to sham TENS (where the machine looks the same but doesn’t deliver a pulse). </p>
<p>This is in line with an older <a href="https://www.cochrane.org/CD002123/MENSTR_transcutaneous-electrical-nerve-stimulation-for-primary-dysmenorrhoea">Cochrane review</a> that found similar benefits. </p>
<p>Pain relieving effects only tend to last while the device is active.</p>
<p><strong>For endometriosis</strong></p>
<p>Endometriosis is where tissue similar to the lining of the uterus is found outside the uterus, commonly in the pelvis. There is only <a href="https://doi.org/10.1016/j.ejogrb.2015.07.009">one</a> study of TENS for pelvic pain due to endometriosis. </p>
<p>This study compared two types of TENS – one using a higher frequency for 20 minutes twice a day, and one using a lower frequency for 30 minutes once per week. Both types used pads placed on the tailbone, and women were told to make the pulses “strong, but comfortable”. </p>
<p>Both types improved pelvic pain, pain after sex, and quality of life, but not period pain. This was a very small study (11 women in each group) and there was no control or placebo group. So we need larger studies with a proper control group before we can be sure if TENS works for endometriosis pain.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/i-have-painful-periods-could-it-be-endometriosis-101026">I have painful periods, could it be endometriosis?</a>
</strong>
</em>
</p>
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<h2>Is it safe?</h2>
<p>Most <a href="https://www.sciencedirect.com/science/article/pii/S155083072030286X">studies</a> report no side effects when the pads are used on the abdomen or lower spine.</p>
<p>However, if you turn up the intensity too high it <a href="https://www.tandfonline.com/doi/full/10.2147/IJWH.S220523">can be uncomfortable</a>. You could also get a rash from the adhesive on the pads.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/first-periods-can-come-as-a-shock-5-ways-to-support-your-kid-when-they-get-theirs-177920">First periods can come as a shock. 5 ways to support your kid when they get theirs</a>
</strong>
</em>
</p>
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<h2>Which one to buy?</h2>
<p>All TENS machines should allow you to change the <em>intensity</em> (how strong the pulse feels). Some also allow you to change the <em>frequency</em> (how often the pulses happen).</p>
<p>If you are going to use the device occasionally (less than 4-5 days per month) you may just need a device that allows you to change the <a href="https://doi.org/10.2522/ptj.20120281">intensity</a>.</p>
<p>To get the best relief, the machine should be turned up high enough so it delivers noticeable pulses, but is not painful. So you need to find your own comfort level.</p>
<p>For period pain, <a href="https://www.tandfonline.com/doi/full/10.2147/IJWH.S220523">high frequency</a> (more than 50 pulses per second) shows better results than low frequency (usually 2-5 pulses per second). So make sure the device you’re thinking of buying is either set to a high frequency or you can change the frequency.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Woman clutching tummy and head lying on sofa" src="https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529242/original/file-20230531-15-mlq5gp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Many people find it hard to manage period pain. So would TENS help?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sick-muslim-woman-hijab-having-acute-1616145232">Shutterstock</a></span>
</figcaption>
</figure>
<p>For people with endometriosis, it’s a little more tricky. You’ll probably going to want to use the device more often than a few days a month. </p>
<p>Unfortunately, like with taking regular opioid painkillers, with regular TENS use people can become <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027071/">tolerant</a> to its pain-relieving effect, which means it doesn’t work as well as it did when you first started using it.</p>
<p>One possible solution to tolerance is to use <a href="https://academic.oup.com/ptj/article/93/10/1397/2735589">mixed-frequency TENS</a> where both high and low frequencies are alternated. You can also slowly increase the intensity level over time. </p>
<p>TENS also doesn’t work well when people are regular <a href="https://pubmed.ncbi.nlm.nih.gov/6965549/">opioid users</a>. This is important as people with endometriosis are often using <a href="https://www.jmig.org/article/S1553-4650(20)30291-0/fulltext">opioid medications</a> to manage their pain. If you are using opioids regularly, high-frequency TENS is likely to be a <a href="https://academic.oup.com/ptj/article/93/10/1397/2735589">better choice</a>.</p><img src="https://counter.theconversation.com/content/201389/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mike Armour does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>TENS machines for period pain are all over social media. But what are they? And do they work?Mike Armour, Associate Professor at NICM Health Research Institute, Western Sydney UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2009812023-05-09T12:24:22Z2023-05-09T12:24:22ZMemories may be stored in the membranes of your neurons<figure><img src="https://images.theconversation.com/files/524523/original/file-20230504-21-f51zke.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2130%2C1406&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Changes in the synapses between neurons is responsible for learning and memory.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/nerve-cells-and-electrical-pulses-royalty-free-illustration/758308889">KTSDESIGN/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Your brain is responsible for controlling most of your body’s activities. Its information processing capabilities are what allow you to learn, and it is the central repository of your memories. But how is memory formed, and where is it located in the brain? </p>
<p>Although neuroscientists have identified <a href="https://courses.lumenlearning.com/waymaker-psychology/chapter/parts-of-the-brain-involved-with-memory/">different regions of the brain</a> where memories are stored, such as the hippocampus in the middle of the brain, the neocortex in the top layer of the brain and the cerebellum at the base of the skull, they have yet to identify the specific molecular structures within those areas involved in memory and learning.</p>
<p>Research from our team of <a href="https://scholar.google.com/citations?user=o_qJUYIAAAAJ&hl=en">biophysicists</a>, <a href="https://scholar.google.com/citations?user=lFqiBd4AAAAJ&hl=en">physical chemists</a> and <a href="https://scholar.google.co.uk/citations?user=2mXI8mUAAAAJ&hl=en">materials scientists</a> suggests that memory might be <a href="https://doi.org/10.1073/pnas.2212195119">located in the membranes of neurons</a>.</p>
<p>Neurons are the fundamental working units of the brain. They are designed to transmit information to other cells, enabling the body to function. The junction between two neurons, called a synapse, and the chemistry that takes place between synapses, in the space called the synaptic cleft, are <a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">responsible for learning and memory</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of neuronal synapse" src="https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=555&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=555&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=555&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=698&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=698&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524518/original/file-20230504-1253-pu06u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=698&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The space between two neurons is called a synapse.</span>
<span class="attribution"><a class="source" href="https://openstax.org/books/anatomy-and-physiology/pages/1-introduction">OpenStax</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>At a more fundamental level, the synapse is made of two membranes: one associated with the presynaptic neuron that transmits information, and one associated with the postsynaptic neuron that receives information. Each membrane is made up of a <a href="https://doi.org/10.1016/j.bpj.2017.10.017">lipid bilayer</a> containing proteins and other biomolecules. </p>
<p>The changes taking place between these two membranes, commonly known as <a href="https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/what-synaptic-plasticity#">synaptic plasticity</a>, are the primary mechanism for learning and memory. These include changes to the amounts of different proteins in the membranes, as well as the structure of the membranes themselves.</p>
<p>Synaptic plasticity can be classified as either being short term, lasting from milliseconds to a few minutes, or long term, lasting from minutes to hours or longer. The chemical processes occurring between the presynaptic and postsynaptic membranes in short-term plasticity eventually lead to long-term synaptic plasticity.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/uVQXZudZd5s?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Long-term potentiation is thought to be the physiological mechanism behind learning.</span></figcaption>
</figure>
<p>Since scientists think the main way the brain processes and stores information is through these <a href="https://doi.org/10.1038/s41539-019-0048-y">long-term changes to the synapses</a>, we wondered if memory might be stored in the membrane’s lipid bilayer.</p>
<p>We found that exposing a model of a simple lipid bilayer to electrical stimulation – not unlike the stimulation used in studies of the brain – can <a href="https://doi.org/10.1073/pnas.2212195119">trigger long-term changes</a>. What made this result unique was that we were able to generate changes in our simple membrane model without the neuronal proteins typically associated with it. Furthermore, long-term plasticity persisted in our model for almost 24 hours without any further electrical stimulation. This suggests that the neuronal membrane may be responsible for memory storage.</p>
<p>Our findings support the use of the lipid bilayer as a model for understanding the molecular basis of biological memory. It may also serve as a platform for <a href="https://theconversation.com/neuronlike-circuits-bring-brainlike-computers-a-step-closer-146659">neuromorphic computing</a>, in which the memory components of a computer are modeled after the structure and function of the human brain.</p>
<p>Finally, the lipid bilayer may also be a potential therapeutic target to treat different neurological conditions. Pinpointing where and how memory is stored in the brain will not only revolutionize how we understand learning and memory, it can also guide the development of new therapies for diseases like Alzheimer’s and Parkinson’s.</p><img src="https://counter.theconversation.com/content/200981/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Patrick Collier receives funding from the Laboratory Directed Research and Development (LDRD) program at Oak Ridge National Laboratory and the Center for Nanophase Sciences (CNMS).</span></em></p><p class="fine-print"><em><span>Dima Bolmatov receives funding from the National Science Foundation, Division of Molecular and Cellular Biosciences (MCB).</span></em></p><p class="fine-print"><em><span>John Katsaras does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Pinpointing where memories are stored in the brain and how they are transmitted could provide new targets to treat neurological diseases and serve as models for neuromorphic computing.John Katsaras, Senior Scientist in Biological Systems at Oak Ridge National Laboratory, Joint Faculty Professor in Physics and Astronomy, University of TennesseeCharles Patrick Collier, Research Scientist in Nanophase Materials Sciences, University of TennesseeDima Bolmatov, Ph.D., Research Assistant Professor in Physics, University of TennesseeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2042592023-04-26T15:12:44Z2023-04-26T15:12:44ZCognitive flexibility is essential to navigating a changing world – new research in mice shows how your brain learns new rules<figure><img src="https://images.theconversation.com/files/522864/original/file-20230425-26-ozwsdf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A class of inhibitory neurons can make long-distance connections across both hemispheres of the brain.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/brain-shape-labyrinth-with-staircase-royalty-free-image/1384468191">akinbostanci/iStock via Getty Images Plus</a></span></figcaption></figure><p>Being flexible and learning to adapt when the world changes is something you practice every day. Whether you run into a new construction site and have to reroute your commute or download a new streaming app and have to relearn how to find your favorite show, changing familiar behaviors in response to new situations is an essential skill.</p>
<p>To make these adaptations, your brain changes its activity patterns within a structure called the <a href="https://doi.org/10.1146/annurev.neuro.24.1.167">prefrontal cortex</a> – an area of the brain critical for cognitive functions such as attention, planning and decision-making. But which specific circuits “tell” the prefrontal cortex to update its activity patterns in order to change behavior have been unknown. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/i47_jiCsBMs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The prefrontal cortex of the brain is involved in executive functions like self-control and decision-making.</span></figcaption>
</figure>
<p>We are a <a href="https://scholar.google.com/citations?user=a-dRpwgAAAAJ&hl=en">team of</a> <a href="https://scholar.google.com/citations?user=EYE8lYIAAAAJ&hl=en">neuroscientists</a> who study how the brain processes information and what happens when this function is impaired. In our newly published research, we discovered a <a href="https://www.nature.com/articles/s41586-023-06012-9">special class of neurons</a> in the prefrontal cortex that may enable flexible behavior and, when they malfunction, may lead to conditions such as schizophrenia and bipolar disorder.</p>
<h2>Inhibitory neurons and learning new rules</h2>
<p><a href="https://www.brainfacts.org/brain-anatomy-and-function/cells-and-circuits/2021/how-inhibitory-neurons-shape-the-brains-code-100621">Inhibitory neurons</a> dampen the activity of other neurons in the brain. Researchers have traditionally assumed they send their electrical and chemical outputs only to nearby neurons. However, we found a particular class of inhibitory neurons in the prefrontal cortex that communicate across long distances to neurons in the opposite hemisphere of the brain.</p>
<p>We wondered whether these long-range inhibitory connections are involved in coordinating changes in activity patterns across the left and right prefrontal cortex. By doing so, they might provide the critical signals that help you change your behavior at the right moment.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of an interneuron" src="https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=923&fit=crop&dpr=1 600w, https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=923&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=923&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1160&fit=crop&dpr=1 754w, https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1160&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/522868/original/file-20230425-22-cg77ik.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1160&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Interneurons connect other neurons together.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/G2ScFK">NICHD/McBain Laboratory via Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>To test the function of these long-range inhibitory connections, we observed mice performing a task that required them to learn a rule to receive a reward and then later adapt to a new rule in order to continue receiving the reward. In this task, mice dug in bowls to find hidden food. Initially, the smell of garlic or the presence of sand within a bowl might indicate the location of the hidden food. The specific cue associated with the reward would later change, forcing the mice to learn a new rule. </p>
<p>We found that silencing the long-range inhibitory connections between the left and right prefrontal cortex <a href="https://www.nature.com/articles/s41586-023-06012-9">caused the mice to get stuck</a>, or perseverate, on one rule and prevented them from learning new ones. They were unable to change gears and learn that the old cue was now meaningless and the new cue signaled food.</p>
<h2>Brain waves and flexible behavior</h2>
<p>We also made surprising discoveries about how these long-range inhibitory connections create behavioral flexibility. Specifically, they synchronize a set of “brain waves” called <a href="https://doi.org/10.1523/jneurosci.0990-16.2016">gamma oscillations</a> across the two hemispheres. Gamma oscillations are rhythmic fluctuations in brain activity that occur roughly 40 times per second. These fluctuations can be detected during many cognitive functions, such as when performing a task that requires holding information in your memory or making different movements based on what you see on a computer screen. </p>
<p>Though scientists have observed the presence of gamma oscillations for many decades, their function has been controversial. Many researchers think that the synchronization of these rhythmic fluctuations across different brain regions doesn’t serve any useful purpose. Others have speculated that synchronization across different brain regions enhances communication between those regions.</p>
<figure>
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<figcaption><span class="caption">Fluctuations in neural activity manifest as brain waves, or neural oscillations.</span></figcaption>
</figure>
<p>We found a completely different potential role for gamma synchrony. When long-range inhibitory connections synchronize gamma oscillations across the left and right prefrontal cortex, they seem to also <a href="https://www.nature.com/articles/s41586-023-06012-9">gate communication between them</a>. When mice learn to disregard a previously established rule that no longer leads to a reward, these connections synchronize gamma oscillations and seem to stop one hemisphere from maintaining unneeded activity patterns in the other. In other words, long-range inhibitory connections seem to stop input from one hemisphere from “getting in the way” of the other when it is trying to learn something new. </p>
<p>For example, the left prefrontal cortex can “remind” the right prefrontal cortex about your usual route to work. But when long-range inhibitory connections synchronize these two areas, they also seem to shut off these reminders and enable new patterns of brain activity corresponding to your new commute to take hold.</p>
<p>Finally, these long-range inhibitory connections also <a href="https://www.nature.com/articles/s41586-023-06012-9">trigger long-lasting effects</a>. Shutting off these connections just once caused mice to have trouble learning new rules several days later. Conversely, rhythmically stimulating these connections to artificially synchronize gamma oscillations can reverse these deficits and restore normal learning.</p>
<h2>Cognitive flexibility and schizophrenia</h2>
<p>Long-range inhibitory connections play an important role in cognitive flexibility. The inability to appropriately update previously learned rules is one <a href="https://pubmed.ncbi.nlm.nih.gov/16965182/">hallmark form of cognitive impairment</a> in psychiatric conditions such as schizophrenia and bipolar disorder. </p>
<p>Research has also seen <a href="https://doi.org/10.1523/jneurosci.0990-16.2016">deficiencies in gamma synchronization</a> and abnormalities in a class of prefrontal inhibitory neurons, which includes the ones we studied, in people with schizophrenia. In this context, our study suggests that treatments that target these long-range inhibitory connections may help improve cognition in people with schizophrenia by synchronizing gamma oscillations.</p>
<p>Many details of how these connections affect brain circuits remain unknown. For example, we do not know exactly which cells within the prefrontal cortex receive input from these long-range inhibitory connections and change their activity patterns to learn new rules. We also do not know whether there are specific molecular pathways that produce the long-lasting changes in neural activity. Answering these questions could reveal how the brain flexibly switches between maintaining and updating old information and potentially lead to new treatments for schizophrenia and other psychiatric conditions.</p><img src="https://counter.theconversation.com/content/204259/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vikaas Sohal receives funding from the National Institutes of Health, the Simons Foundation Autism Research Initiative, the UCSF Dolby Family Center for Mood Disorders, and the Bay Area Psychedelic Research consortium.</span></em></p><p class="fine-print"><em><span>Kathleen Cho receives funding from the Institut national de la santé et de la recherche médicale (Inserm) and the Marie Skłodowska-Curie Individual Fellowship (MSCA-IF). </span></em></p>Learning new rules requires the suppression of old ones. A better understanding of the brain circuits involved in behavioral adaptation could lead to new ways to treat schizophrenia and bipolar disorder.Vikaas Sohal, Professor of Psychiatry, University of California, San FranciscoKathleen Cho, Principal Investigator in Neuroscience, InsermLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2041152023-04-21T21:15:28Z2023-04-21T21:15:28ZNetworks of silver nanowires seem to learn and remember, much like our brains<figure><img src="https://images.theconversation.com/files/522255/original/file-20230421-1579-qs4r3k.jpeg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C2000&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Over the past year or so, generative AI models such as ChatGPT and DALL-E have made it possible to produce vast quantities of apparently human-like, high-quality creative content from a simple series of prompts.</p>
<p>Though highly capable – far outperforming humans in big-data pattern recognition tasks in particular – current AI systems are not intelligent in the same way we are. AI systems aren’t structured like our brains and don’t learn the same way.</p>
<p>AI systems also use <em>vast</em> amounts of energy and resources for training (compared to our three-or-so meals a day). Their ability to adapt and function in dynamic, hard-to-predict and noisy environments is poor in comparison to ours, and they lack human-like memory capabilities.</p>
<p>Our research explores non-biological systems that are more like human brains. In <a href="https://www.science.org/doi/10.1126/sciadv.adg3289">a new study</a> published in Science Advances, we found self-organising networks of tiny silver wires appear to learn and remember in much the same way as the thinking hardware in our heads.</p>
<h2>Imitating the brain</h2>
<p>Our work is part of a field of research called neuromorphics, which aims to replicate the structure and functionality of biological neurons and synapses in non-biological systems.</p>
<p>Our research focuses on a system that uses a network of “nanowires” to mimic the neurons and synapses in the brain. These nanowires are tiny wires about one thousandth the width of a human hair. They are made of a highly conductive metal, such as silver, typically coated in an insulating material like plastic. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&rect=118%2C111%2C1111%2C833&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=321&fit=crop&dpr=1 754w, https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=321&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/522056/original/file-20230420-18-hczxem.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=321&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Left: microscope image of silver nanowire networks, from our Science Advances paper. Right: strengthened and pruned (weakened) pathways in nanowire networks.</span>
</figcaption>
</figure>
<p>Nanowires self-assemble to form a network structure similar to a biological neural network. Like neurons, which have an insulating membrane, each metal nanowire is coated with a thin insulating layer. </p>
<p>When we stimulate nanowires with electrical signals, ions migrate across the insulating layer and into a neighbouring nanowire (much like neurotransmitters across synapses). As a result, we observe synapse-like electrical signalling in nanowire networks.</p>
<h2>Learning and memory</h2>
<p>Our new work uses this nanowire system to explore the question of human-like intelligence. Central to our investigation are two features indicative of high-order cognitive function: learning and memory. </p>
<p>Our study demonstrates we can selectively strengthen (and weaken) synaptic pathways in nanowire networks. This is similar to “<a href="https://www.jneurosci.org/content/14/7/3985">supervised learning</a>” in the brain. In this process, the output of synapses is compared to a desired result. Then the synapses are strengthened (if their output is close to the desired result) or pruned (if their output is not close to the desired result).</p>
<p>We expanded on this result by showing we could increase the amount of strengthening by “rewarding” or “punishing” the network. This process is inspired by “<a href="https://www.sciencedirect.com/science/article/abs/pii/S0022249608001181">reinforcement learning</a>” in the brain.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/neuronlike-circuits-bring-brainlike-computers-a-step-closer-146659">Neuronlike circuits bring brainlike computers a step closer</a>
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</em>
</p>
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<p>We also implemented a version of a test called the “<a href="https://www.tandfonline.com/doi/abs/10.1080/09658211003702171"><em>n</em>-back task</a>” which is used to measure working memory in humans. It involves presenting a series of stimuli and comparing each new entry with one that occurred some number of steps (<em>n</em>) ago.</p>
<p>The network “remembered” previous signals for at least seven steps. Curiously, seven is often regarded as the <a href="https://psycnet.apa.org/record/1957-02914-001">average number of items</a> humans can keep in working memory at one time.</p>
<p>When we used reinforcement learning, we saw dramatic improvements in the network’s memory performance. </p>
<p>In our nanowire networks, we found the formation of synaptic pathways depends on how those synapses have been activated in the past. This is also the case for synapses in the brain, where neuroscientists call it “<a href="https://www.sciencedirect.com/science/article/abs/pii/S016622369680018X?via%3Dihub">metaplasticity</a>”. </p>
<h2>Synthetic intelligence</h2>
<p>Human intelligence is still likely a long way from being replicated. </p>
<p>Nonetheless, our research on neuromorphic nanowire networks shows it is possible to implement features essential for intelligence – such as learning and memory – in non-biological, physical hardware. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/five-ways-the-superintelligence-revolution-might-happen-32124">Five ways the superintelligence revolution might happen</a>
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<p>Nanowire networks are different from the artificial neural networks used in AI. Still, they may lead to so-called “synthetic intelligence”.</p>
<p>Perhaps a neuromorphic nanowire network could one day learn to have conversations that are more human-like than ChatGPT, and remember them.</p><img src="https://counter.theconversation.com/content/204115/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Zdenka Kuncic owns shares in Emergentia, Inc.</span></em></p><p class="fine-print"><em><span>Alon Loeffler does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Collections of self-organising nanowires behave a lot like the neurons and synapses in our brains, with startling results.Alon Loeffler, PhD researcher, University of SydneyZdenka Kuncic, Professor of Physics, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2027002023-03-29T14:36:40Z2023-03-29T14:36:40ZThese neurons are the reason you yawn when you see others do it – and they could help us teach children more creatively too<figure><img src="https://images.theconversation.com/files/518004/original/file-20230328-28-h1o927.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C1991%2C1329&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Watching this one-year old going to sleep might make you want to go to sleep too.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/es/image-photo/one-year-old-baby-girl-boy-1649094604">Shutterstock</a></span></figcaption></figure><p>Have you ever wondered why when we see someone yawn, we yawn almost immediately? Or how newborns imitate facial gestures like sticking out their tongue? And what about how we learn to use scissors or to colour?</p>
<p>It all has a lot to do with a particular type of neuron called “mirror neurons”.</p>
<h2>What are mirror neurons?</h2>
<p>Mirror neurons are amazing neurons that participate in important processes such as learning, empathy and imitation.</p>
<p>They were discovered by chance by the Italian neurobiologist <a href="https://www.sciencedirect.com/science/article/abs/pii/0926641095000380">Giacomo Rizzolatti in 1996</a>. Looking at the brain of a macaque, Rizzolatti and his team recorded neurons that were activated not only when the animal carried out an action, but also when it observed another animal doing the same activity. What’s more, in both cases the premotor cortex was activated in an identical way.</p>
<p>It was soon found that exactly the same thing happens in humans. For example, when we watch someone climb stairs, the motor neurons that correspond to those movements are activated without us taking a single step. When we observe another individual performing an action, without even having to speak, our mirror neurons can put us <a href="https://www.cambridge.org/core/journals/behavioral-and-brain-sciences/article/abs/mirror-neurons-from-origin-to-function/A376CF4E7269CADFCD9D563A39ADEDC0">in the same situation</a>, simulating the action mentally as if it were happening to us.</p>
<p>This type of nerve cell even enables us to understand the intention with which an action is carried out.</p>
<p>Another of mirror neurons’ properties is that they are activated by the sound associated with an action. For example, when they hear paper being torn, they mentally emulate that action – even if we do not actually see it taking place.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/476595/original/file-20220728-11927-znqh4c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<h2>Where are they?</h2>
<p>Mirror neurons are located in <a href="https://www.cell.com/trends/cognitive-sciences/fulltext/S1364-6613(22)00134-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1364661322001346%3Fshowall%3Dtrue">four brain regions that communicate with each other</a>: the premotor area, the inferior frontal gyrus, the parietal lobe, and the superior temporal sulcus. Each of these is responsible for a different function:</p>
<ul>
<li><p>The premotor area manages movements and controls muscles</p></li>
<li><p>The inferior frontal gyrus is involved in executive control processes, the management of social and affective behaviours and decision making</p></li>
<li><p>The parietal lobe analyses visual sensory information</p></li>
<li><p>The superior temporal sulcus is involved in auditory processing and language.</p></li>
</ul>
<h2>Learning and empathy</h2>
<p>The existence of mirror neurons is <a href="https://www.nature.com/articles/nrn.2016.135">essential for our species</a>. That’s mainly because of the role they play in learning by imitation and observation but also because they participate in language acquisition and are essential in the development of <a href="https://www.pnas.org/doi/10.1073/pnas.0902666106">empathy</a> and social behaviour – they allow us to understand the actions of other people and their emotions.</p>
<p>Mirror neurons are implicated in numerous clinical conditions. They are affected by autism, schizophrenia, apraxia (an inability to perform motor tasks) and neurodegenerative diseases, <a href="https://onlinelibrary.wiley.com/doi/10.1002/jnr.24579">among others</a>.</p>
<p>For example, in autism, there are motor, language and social problems that coexist. It is no coincidence that all these functions are related to brain areas where mirror neurons are located.</p>
<h2>Harnessing mirror neurons in the classroom</h2>
<p>We can consider observational learning to be any moment in which an action is observed and something new is learned or previous knowledge is modified. We must not confuse imitation (for example, copying an individual’s gestures) with <a href="https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(21)00020-5">observational learning</a>. The latter is a change that lasts in the individual and produces a response.</p>
<p>By observing a process, mirror neurons prepare us to imitate the action being observed. If, while teaching, we combine observational learning with student creativity, we will obtain more efficient learning. The lesson will be internalised and will last over time.</p>
<p>All of this leads us to highlight the important role that educators play in the classroom. The students observe all the actions carried out by their <a href="https://link.springer.com/article/10.1007/s10648-008-9094-3">teacher</a>. For this reason, we should look beyond traditional teaching (which is merely expository and static in nature) and carry out more activities that allow for observation skills to be developed.</p>
<p>Another aspect to highlight is the attitude that teachers have in the classroom. Mirror neurons allow us to understand the intentions and <a href="https://revistas.uam.es/didacticasespecificas/article/view/8697">emotions being transmitted</a>. Those passionate teachers who teach their subjects with enthusiasm and joy achieve a greater level of concentration and observation from the student, capturing their attention for a longer amounts of time and infecting them with their emotion.</p>
<p>For all these reasons, there are different educational methodologies that allow us to combine this knowledge about mirror neurons with useful tools that fit into the classroom context. In any case, it is essential to incorporate new strategies to encourage motivation, as well as to use <a href="https://revistas.uca.es/index.php/eureka/article/view/2613">manipulative tasks</a> (laboratory sessions, practical cases, etc.) that allow the contents being learned to be used and internalised.</p>
<p>All the events that take place in the classroom, the dynamics of the classes and the emotional aspects that the teacher transmits to the students will condition the learning and experience that the students have in the classroom.</p><img src="https://counter.theconversation.com/content/202700/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Las personas firmantes no son asalariadas, ni consultoras, ni poseen acciones, ni reciben financiación de ninguna compañía u organización que pueda obtener beneficio de este artículo, y han declarado carecer de vínculos relevantes más allá del cargo académico citado anteriormente.</span></em></p>Mirror neurons play a fundamental role in learning by imitation and observation or empathy. This is why we should take them into account when developing new educational tools.Laura Trujillo Estrada, Profesora Ayudante Doctora. Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga. Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED). Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de MálagaAgustina María Torres Prioris, Profesor Sustituto Interino en el Departamento de Didáctica de la Matemática, de las Ciencias Sociales y de las Ciencias Experimentales, Universidad de Málaga. Miembro del Grupo de Investigación en Enseñanza de las Ciencias y Competencias (ENCIC), Universidad de MálagaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2011492023-03-29T12:28:19Z2023-03-29T12:28:19ZBrains also have supply chain issues – blood flows where it can, and neurons must make do with what they get<figure><img src="https://images.theconversation.com/files/516713/original/file-20230321-20-at1818.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1921%2C1561&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Blood carries oxygen and vital nutrients to the brain.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cerebral-angiography-image-from-fluoroscopy-in-royalty-free-image/1473413961">Mr. Suphachai Praserdumrongchai/iStock via Getty Images</a></span></figcaption></figure><p><a href="https://doi.org/10.3389/fnint.2022.818685">Neuroscientists have long assumed</a> that neurons are greedy, hungry units that demand more energy when they become more active, and the circulatory system complies by providing as much blood as they require to fuel their activity. Indeed, as neuronal activity increases in response to a task, blood flow to that part of the brain increases even more than its rate of energy use, leading to a surplus. This increase is the basis of common <a href="https://doi.org/10.3389/fnint.2022.818685">functional imaging technology</a> that generates colored maps of brain activity.</p>
<p>Scientists used to interpret this apparent mismatch in blood flow and energy demand as evidence that there is no shortage of blood supply to the brain. The idea of a nonlimited supply was based on the observation that <a href="https://doi.org/10.1038%2Fjcbfm.2013.181">only about 40% of the oxygen</a> delivered to each part of the brain is used – and this percentage actually drops as parts of the brain become more active. It seemed to make evolutionary sense: The brain would have evolved this faster-than-needed increase in blood flow as a safety feature that guarantees sufficient oxygen delivery at all times.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/B10pc0Kizsc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Functional magnetic resonance imaging is one of several ways to measure the brain.</span></figcaption>
</figure>
<p>But does blood distribution in the brain actually support a demand-based system? <a href="https://scholar.google.com.br/citations?user=cldyZo8AAAAJ&hl=en">As a neuroscientist myself</a>, I had previously examined a number of other assumptions about the most basic facts about brains and found that they didn’t pan out. To name a few: Human brains <a href="https://doi.org/10.1002/cne.21974">don’t have 100 billion neurons</a>, though they do <a href="https://doi.org/10.3389/fnana.2014.00046">have the most cortical neurons</a> of any species; the <a href="https://doi.org/10.1126/science.aaa9101">degree of folding of the cerebral cortex</a> does not indicate how many neurons are present; and it’s not larger animals that live longer, but <a href="https://doi.org/10.1002/cne.24564">those with more neurons in their cortex</a>.</p>
<p>I believe that figuring out what determines blood supply to the brain is essential to understanding how brains work in health and disease. It’s like how cities need to figure out whether the current electrical grid will be enough to support a future population increase. Brains, like cities, only work if they have enough energy supplied.</p>
<h2>Resources as highways or rivers</h2>
<p>But how could I test whether blood flow to the brain is truly demand-based? My freezers were stocked with preserved, dead brains. How do you study energy use in a brain that is not using energy anymore?</p>
<p>Luckily, the brain leaves behind evidence of its energy use through the pattern of the vessels that distribute blood throughout it. I figured I could look at the <a href="https://doi.org/10.3389/fnint.2022.760887">density of capillaries</a> – the thin, one-cell-wide vessels that transfer gases, glucose and metabolites between brain and blood. These capillary networks would be preserved in the brains in my freezers.</p>
<p>A demand-based brain should be comparable to a road system. If arteries and veins are the major highways that carry goods to the town of specific parts of the brain, capillaries are akin to the neighborhood streets that actually deliver goods to their final users: individual neurons and the cells that work with them. Streets and highways are built on demand, and a road map shows what a demand-based system looks like: Roads are often concentrated in parts of the country where there are more people – the energy-guzzling units of society.</p>
<p>In contrast, a supply-limited brain should look like the river beds of a country, which couldn’t care less about where people are located. Water will flow where it can, and cities just have to adjust and make do with what they can get. Chances are, cities will form in the vicinity of the main arteries – but absent major, purposeful remodeling, their growth and activities are limited by how much water is available.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of astrocytes contacting a capillary" src="https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=383&fit=crop&dpr=1 600w, https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=383&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=383&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=482&fit=crop&dpr=1 754w, https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=482&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/516731/original/file-20230321-2166-um4qs4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=482&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This image shows astrocytes, a type of brain cell, contacting a ravinelike capillary.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/astrocyte-in-the-brain-touching-a-capillary-250x-royalty-free-image/152883277">Ed Reschke/Stone via Getty Images</a></span>
</figcaption>
</figure>
<p>Would I find that capillaries are concentrated in parts of the brain with more neurons and supposedly require more energy, like streets and highways built in a demand-based manner? Or would I find that they are more like creeks and streams that permeate the land where they can, oblivious to where the most people are, in a supply-driven manner?</p>
<p>What I found was clear evidence for the latter. For <a href="https://doi.org/10.3389/fnint.2022.760887">both mice</a> <a href="https://doi.org/10.3389/fnint.2022.821850">and rats</a>, capillary density makes up a meager 2% to 4% of brain volume, regardless of how many neurons or synapses are present. Blood flows in the brain like water down rivers: where it can, not where it is needed.</p>
<p>If blood flows regardless of need, this implies that the brain actually uses blood as it is supplied. We found that the tiny variations in capillary density across different parts of dead rat brains matched perfectly with the rates of blood flow and energy use in the same parts of other living rat brains that researchers measured 15 years prior. </p>
<h2>Resolving blood flow and energy demand</h2>
<p>Could the specific density of capillaries in each part of the brain be so limiting that it dictates how much energy that part uses? And would that apply to the brain as a whole?</p>
<p>I partnered with my colleague <a href="https://scholar.google.com/citations?user=18-0e2EAAAAJ&hl=en">Doug Rothman</a> to answer these questions. Together, we discovered that not only do both human and rat brains do what they can with what blood they get and typically work at about 85% capacity, but overall brain activity is indeed <a href="https://doi.org/10.3389/fnint.2022.818685">dictated by capillary density</a>, all else being equal. </p>
<p>The reason why only 40% of the oxygen supplied to the brain actually gets used is because this is the maximum amount that can be exchanged as blood flows by – like workers trying to pick up items on an assembly line going too fast. Local arteries can deliver more blood to neurons if they start using slightly more oxygen, but this comes at the cost of diverting blood away from other parts of the brain. Since gas exchange was already near full capacity to begin with, the fraction of oxygen extraction seems to even drop with a slight increase in delivery.</p>
<p>From afar, energy use in the brain may look demand-based – but it really is supply-limited.</p>
<h2>Blood supply influences brain activity</h2>
<p>So why does any of this matter?</p>
<p>Our findings offer a possible explanation for why the brain can’t truly multitask – only quickly alternate between focuses. Because blood flow to the entire brain is tightly regulated and remains essentially constant throughout the day as you alternate between activities, our research suggests that any part of the brain that experiences an increase in activity – because you start doing math or playing a song, for example – can only get slightly more blood flow at the expense of diverting blood flow from other parts of the brain. Thus, the <a href="https://doi.org/10.1126/science.1183614">inability to do two things at the same time</a> might have its origins in blood flow to the brain being supply-limited, not demand-based. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="MRI brain scan images" src="https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=727&fit=crop&dpr=1 600w, https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=727&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=727&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=914&fit=crop&dpr=1 754w, https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=914&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/516735/original/file-20230321-2077-i19xsb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=914&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A better understanding of how the brain works could offer insights into human behavior and disease.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/brain-scan-close-up-royalty-free-image/sb10069835m-001">Peter Dazeley/The Image Bank via Getty Images</a></span>
</figcaption>
</figure>
<p>Our findings also offer insight into aging. If neurons must make do with what energy they can get from a mostly constant blood supply, then the parts of the brain with the highest densities of neurons will be the first to be affected when there is a shortage – just like the largest cities feel the pain of a drought before smaller ones. </p>
<p>In the cortex, the parts with the <a href="https://doi.org/10.3389/fnint.2022.821850">highest neuron densities</a> are the hippocampus and entorhinal cortex. These areas are involved in short-term memory and the <a href="https://doi.org/10.1212%2F01.wnl.0000106462.72282.90">first to suffer in aging</a>. More research is needed to test whether the parts of the brain most vulnerable to aging and disease are the ones with the greatest number of neurons packed together and competing for a limited blood supply. </p>
<p>If it’s true that capillaries, like neurons, <a href="https://doi.org/10.1016/j.cmet.2019.05.010">last a lifetime</a> in humans as they do in lab mice, then they may play a bigger role in brain health than expected. To make sure your brain neurons remain healthy in old age, taking care of the capillaries that keep them supplied with blood may be a good bet. The good news is that there are two proven ways to do this: a <a href="https://doi.org/10.1001/archneurol.2011.548">healthy diet</a> and <a href="https://doi.org/10.18632/aging.103046">exercise</a>, which are never too late to begin.</p><img src="https://counter.theconversation.com/content/201149/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Suzana Herculano-Houzel does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Neuroscientists have typically thought of energy supply to the brain as demand-based. A supply-limited view offers another perspective toward aging and why multitasking can be difficult.Suzana Herculano-Houzel, Associate Professor of Psychology, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2008312023-03-07T19:06:07Z2023-03-07T19:06:07ZElectricity flow in the human brain can be predicted using the simple maths of networks, new study reveals<figure><img src="https://images.theconversation.com/files/513515/original/file-20230305-22-d2bpkt.jpg?ixlib=rb-1.1.0&rect=173%2C101%2C3682%2C2395&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Ravil Sayfullin/Shutterstock</span></span></figcaption></figure><p>Through a vast network of nerve fibres, electrical signals are constantly travelling across the brain. This complicated activity is what ultimately gives rise to our thoughts, emotions and behaviours – but also possibly to mental health and neurological problems <a href="https://www.nature.com/articles/s41583-019-0177-6">when things go wrong</a>.</p>
<p>Brain stimulation is an <a href="https://www.sciencedirect.com/science/article/pii/S1388245719312799">emerging treatment</a> for such disorders. Stimulating a region of your brain with electrical or magnetic pulses will trigger a cascade of signals through your network of nerve connections.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-repetitive-transcranial-magnetic-stimulation-and-how-does-it-actually-work-160771">What is repetitive transcranial magnetic stimulation and how does it actually work?</a>
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</em>
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<hr>
<p>However, at the moment, scientists are not quite sure how these cascades travel to impact the activity of your brain as a whole – an important missing piece that limits the benefits of brain stimulation therapies.</p>
<p>In our latest research, <a href="https://www.cell.com/neuron/fulltext/S0896-6273(23)00077-6">published in Neuron today</a>, we discovered the spread of brain stimulation can be predicted using the mathematics of networks.</p>
<h2>Tracking electrical signals in the brain</h2>
<p>Studying communication in the human brain is hard. This is because electrical signals move very fast, at the scale of thousandths of a second, between one part of the brain and another.</p>
<p>To make matters more complicated, signals are communicated via an incredibly complex network of nerve fibres that interlinks all brain regions. These issues make it difficult for scientists to even observe signals travelling through the brain.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/like-sightseeing-in-paris-a-new-model-for-brain-communication-96983">Like sightseeing in Paris – a new model for brain communication</a>
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</em>
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<hr>
<p>However, under very special and controlled circumstances, we can use invasive electrodes to precisely track the propagation of brain signals. Invasive electrodes are instruments that are surgically inserted into the brains of consenting patients.</p>
<p>It is important to stress this type of invasive procedure can only be done in very special circumstances, when the primary goal is to help patients. In our case, patients were people with severe epilepsy. When epilepsy patients do not respond to medication, they can opt to use electrodes to help doctors find out more about what might be happening in their brains.</p>
<p>Our study was based on <a href="https://f-tract.eu/">a large group of 550 epilepsy patient volunteers</a> in more than 20 hospitals across North America, Asia and Europe.</p>
<p>The electrodes provide a way to gently stimulate a brain area with an electrical pulse, and, at the same time, record the patient’s brain activity. We used data from electrodes placed in different positions of the brain to track the communication of electrical pulses from one region to another.</p>
<p>As a last ingredient for our study, we used MRI scans to reconstruct the network of nerve fibres of the human brain, known as the <a href="https://en.wikipedia.org/wiki/Connectome">connectome</a>. This gave us a model of the physical wiring through which electrical signals are communicated in the brain.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three colourful images of the human brain in various stages of abstraction" src="https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=228&fit=crop&dpr=1 600w, https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=228&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=228&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=287&fit=crop&dpr=1 754w, https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=287&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/513308/original/file-20230302-19-o6mch8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=287&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are three steps in constructing a model of the connectome. First, we consider the human brain’s anatomy. Then, we use MRI scans to create a 3D model of all nerve connection fibres. Lastly, we reconstruct the brain’s wiring network and use it to understand communication between brain regions.</span>
<span class="attribution"><span class="source">Left: Wikimedia Commons. Centre and right: author provided.</span></span>
</figcaption>
</figure>
<h2>The mathematics of network communication</h2>
<p>So, how are signals communicated via the complex wiring of the connectome?</p>
<p>A simple possibility is signals travel via the most direct paths in the connectome. In network terms, this would mean that an electrical pulse goes from one region to another via the shortest path of intermediate regions between them.</p>
<p>Another idea is that signals spread via <a href="https://www.nature.com/articles/nrn.2017.149">network diffusion</a>. To understand this, think about how water would flow down a network of pipes.</p>
<p>Each time the water reaches a junction in the network, the flow is split along diverging paths. More junctions along the water’s journey means more splits, and the flow along any given path becomes weaker. However, if some of the diverging paths meet again downstream, the strength of the flow increases again. In this analogy, all connections (pipes) in the network contribute to shaping signal (water) flow, not only the ones along the most direct path.</p>
<h2>What we found</h2>
<p>These two types of network communication – shortest paths versus diffusive flow – are <a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006833">two competing hypotheses</a> to explain how electrical signals cascade through the wiring of the connectome after brain stimulation. Today, scientists are not sure which hypothesis best matches what happens in the brain.</p>
<p>Our study is one of the first to try to settle this debate. To do this, we asked whether shortest paths or diffusion best predict electrical signal propagation, as measured by the electrodes in the brains of the patients.</p>
<p>After analysing the data, we found evidence supporting the diffusive flow hypothesis. This means that many more nerve connections – compared to just the ones travelling along shortest paths – shape how brain stimulation cascades down the connectome.</p>
<p>This is important information for scientists, as it helps us understand how the physical wiring of nerve connections contributes to brain activity and function.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/your-brain-has-landmarks-that-drive-neural-traffic-and-help-you-make-hard-decisions-123751">Your brain has 'landmarks' that drive neural traffic and help you make hard decisions</a>
</strong>
</em>
</p>
<hr>
<h2>What’s next?</h2>
<p>Our study is one of the first of its kind and more work is necessary to confirm what we found. We hope that progress in our understanding of brain communication will also help clinical scientists to <a href="https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2773578">design better brain stimulation treatments</a> for mental health problems. </p>
<p>Brain stimulation can help to “restore” the malfunctioning communication between brain regions. For example, non-invasive stimulation (done outside the skull and without the need for surgery) is a <a href="https://theconversation.com/what-is-repetitive-transcranial-magnetic-stimulation-and-how-does-it-actually-work-160771">treatment for major depressive disorder available in Australia</a>.</p>
<p>In our future research, we will investigate if the discoveries reported here can be used to improve the therapeutic benefit of such brain stimulation treatments.</p><img src="https://counter.theconversation.com/content/200831/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Caio Seguin has received funding from the University of Melbourne. </span></em></p><p class="fine-print"><em><span>Andrew Zalesky receives funding from the Rebecca L. Cooper Foundation, the NHMRC and the ARC. </span></em></p>Your thoughts, emotions and behaviours arise from the complex network of electric activity in your brain. But what can we do when we need to tweak it?Caio Seguin, Postdoctoral research fellow, Indiana UniversityAndrew Zalesky, Professor of Biomedical Engineering and Psychiatry, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1911552023-03-06T13:34:47Z2023-03-06T13:34:47ZHow does RNA know where to go in the city of the cell? Using cellular ZIP codes and postal carrier routes<figure><img src="https://images.theconversation.com/files/510384/original/file-20230215-22-fap759.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cells move their genetic material from one place to another in the form of RNA.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/ribonucleic-acid-strand-illustration-royalty-free-illustration/1395711573">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Before 2020, when my friends and acquaintances asked me what I study <a href="https://scholar.google.com/citations?user=P6al_I8AAAAJ&hl=en">as a molecular biologist</a>, their eyes would inevitably glaze over as soon as I said “RNA.” Now, as the COVID-19 pandemic has shown the power and promise of this molecule to the world at large, their eyes widen. </p>
<p>Despite growing recognition of the importance of RNA, how these molecules get to where they need to be within cells remains largely a mystery.</p>
<p><a href="https://www.genome.gov/genetics-glossary/RNA-Ribonucleic-Acid">RNA</a> is a chemical cousin of DNA. It plays many roles in the cell, but perhaps it’s most well-known as the relay messenger of genetic information. RNA takes a copy of the information in DNA from its storehouse in the nucleus to sites in the cell where this information is decoded to create the building blocks – <a href="https://www.genome.gov/genetics-glossary/Protein">proteins</a> – that make cells what they are. This transport process is <a href="https://doi.org/10.1016/0092-8674(91)90137-N">critical for animal development</a>, and its dysfunction is linked to a variety of <a href="https://doi.org/10.1523/JNEUROSCI.2352-16.2016">genetic diseases in people</a>. </p>
<p>In some ways, cells are like cities, with proteins carrying out specific functions in the “districts” they occupy. Having the right components at the right time and place is essential.</p>
<p>For example, it makes little sense to put a high-security vault in the fashion district. Instead, it needs to be in the financial district, where there are tellers to fill it with currency. Similarly, proteins devoted to energy production for the cell are most functional not when they are confined to the nucleus but when they are in the cell’s power plant, the mitochondria, surrounded by the raw materials and accessories needed for their job.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/cj8dDTHGJBY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The inside of a cell is much like a city.</span></figcaption>
</figure>
<p>So how do cells ensure the millions of proteins they contain are where they are supposed to be? One way is as simple as it sounds: transport them directly. However, every transport step costs energy. Dragging a heavy vault across town isn’t easy. An alternative strategy is to instead take the instructions for making the vault directly to the bank so it’s already in the correct location immediately after construction. </p>
<p>The instructions for making a given protein are contained within RNA. One way to ensure proteins are where they are supposed to be is to transport their RNA blueprint to where their specific functions are needed. But how does RNA get where it needs to be?</p>
<p>My research team focuses on this very question: What are the molecular mechanisms that control RNA transport? Our recently published research hints that some of the <a href="https://doi.org/10.1093/nar/gkac763">molecular language</a> governing this process may be universal <a href="https://doi.org/10.7554/eLife.80040">across all cell types</a>.</p>
<h2>The molecular language of RNA transport</h2>
<p>For a handful of mRNAs – or RNA sequences coding for specific proteins – researchers have an idea about how they’re transported. They often contain a particular string of <a href="https://www.genome.gov/genetics-glossary/Nucleotide">nucleotides</a>, the chemical building blocks that make up RNA, that tell cells about their desired destination. These sequences of nucleotides, or what scientists refer to as RNA “<a href="https://doi.org/10.1111/tra.12730">ZIP codes</a>,” are recognized by proteins that act like mail carriers and deliver the RNAs to where they are supposed to go.</p>
<p>My team and I set out to discover new ZIP codes that <a href="https://doi.org/10.1093/nar/gkac763">send RNAs to neurites</a>, the precursors to the axons and dendrites on neurons that transmit and receive electrical signals. We reasoned that these ZIP codes must lie somewhere within the thousands of nucleotides that make up the RNAs in neurites. But how could we find our ZIP code needle in the RNA haystack?</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/hr8-ZWmVG0Y?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Neurites are long, thin branches extending from the body of a neuron.</span></figcaption>
</figure>
<p>We started by breaking eight mouse neurite-localized RNAs into about 10,000 smaller chunks, each about 250 nucleotides long. We then appended each of these chunks to an unrelated firefly RNA that mouse cells are unlikely to recognize, and watched for chunks that caused the firefly RNA to be transported to neurites. To extend the mail analogy, we took 10,000 blank envelopes (firefly RNAs) and wrote a different ZIP code (pieces of neurite-localized RNA) on each one. By observing which envelopes were delivered to neurites, we were able to discover many new neurite ZIP codes.</p>
<p>We still didn’t know the identity of the protein that acted as the “mail carrier,” however. To figure this out, we purified RNAs containing the newly identified ZIP codes and observed what proteins were purified along with them. The idea was to catch the mail carrier in the act of transport while bound to its target RNA.</p>
<p>We found that one protein that regulates neurite production, named <a href="https://doi.org/10.1101%2Fgad.258483.115">Unkempt</a>, repeatedly appeared with ZIP code-containing RNAs. When we depleted cells of Unkempt, the ZIP codes were no longer able to direct RNA transport to neurites, implicating Unkempt as the “mail carrier” that delivered these RNAs.</p>
<h2>Toward a universal language</h2>
<p>With this work, we identified ZIP codes that sent RNAs to neurites (in our analogy, the bank). But where would an RNA containing one of these ZIP codes end up if it were in a cell that didn’t have neurites (a city that didn’t have a bank)? </p>
<p>To answer this, we looked at where RNAs were in a <a href="https://doi.org/10.7554/eLife.80040">completely different cell type, epithelial cells</a> that line the body’s organs. Interestingly, the same ZIP codes that sent RNAs to neurites sent them to the bottom of epithelial cells. This time we identified another mail carrier, a protein called LARP1, responsible for the transport of RNAs containing a particular ZIP code to both neurites and the bottom end of epithelial cells.</p>
<p>How could one ZIP code and mail carrier transport an RNA to two different locations in two very different cells? It turns out that both of these cell types contain structures called microtubules that are oriented in a very particular way. Microtubules can be thought of as cellular streets that serve as tracks to transport a variety of cargo in the cell. Importantly, these microtubules are polarized, meaning they have ingrained “plus” and “minus” ends. Cargo can therefore be transported in specific directions by targeting to one of these ends.</p>
<figure>
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<figcaption><span class="caption">Microtubules are the roads proteins called kinesin use to transport materials from one cellular location to another.</span></figcaption>
</figure>
<p>In neurons, microtubules stretch through to and have their plus ends at the neurite tip. In epithelial cells, microtubules run from top to bottom, with their plus ends toward the bottom. Given that both of these locations are associated with the plus ends of microtubules, is that why we saw one ZIP code direct RNAs to both of these areas?</p>
<p>To test this, we inhibited the cell’s ability to transport cargo to the plus end of microtubules and monitored whether our ZIP code-containing RNAs were delivered. We found that these RNAs made it to neither the neurites in neurons nor to the bottom end of epithelial cells. This confirmed the role of microtubules in the transport of RNAs containing these particular ZIP codes. Rather than directing RNA to go to specific locations in the cell, these ZIP codes direct RNA to go to the plus ends of microtubules, wherever that might be in a given cell type.</p>
<p>We could compare this process to a mailing address. While the top line (“The Bank”) tells us the name of the building, it’s really the address and street name (“150 Maple Street”) that contains actionable information for the mail carrier. These RNA ZIP codes send RNAs to specific places along microtubule streets, not to specific structures in the cell. This allows for a more flexible yet uniform code, as not all cells share the same structures.</p>
<h2>Moving mRNA into the clinic</h2>
<p>Our research uncovers a new piece of how ZIP code sequences and proteins work together to get RNAs where they need to be. Our findings and methods can also be generalized to discover other new facets of the genetic ZIP code that direct RNAs to other locations in the cell.</p>
<p>Understanding how ZIP code sequences work can help researchers design RNAs that deliver their payload instructions to precise locations in the cell. Given the <a href="https://doi.org/10.1016/j.biotechadv.2020.107534">growing promise of RNA-based therapeutics</a>, ranging from vaccines to cancer therapies, knowing how to make an RNA go from point A to point B is more important than ever.</p><img src="https://counter.theconversation.com/content/191155/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Taliaferro receives funding from the National Institutes of Health and the W.M. Keck Foundation. </span></em></p>Making sure RNA molecules are in the right place at the right time in a cell is critical to development and normal function. Researchers are figuring out exactly how they get to where they need to go.Matthew Taliaferro, Assistant Professor of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1908702023-02-23T13:15:04Z2023-02-23T13:15:04ZImagination makes us human – this unique ability to envision what doesn’t exist has a long evolutionary history<figure><img src="https://images.theconversation.com/files/510729/original/file-20230216-24-yo82dh.jpg?ixlib=rb-1.1.0&rect=102%2C53%2C3346%2C2522&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Your brain can imagine things that haven't happened or that don't even exist.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/constellation-of-you-royalty-free-image/487364203">agsandrew/iStock via Getty Images Plus</a></span></figcaption></figure><p>You can easily picture yourself riding a bicycle across the sky even though that’s not something that can actually happen. You can envision yourself doing something you’ve never done before – like water skiing – and maybe even imagine a better way to do it than anyone else.</p>
<p>Imagination involves creating a mental image of something that is not present for your senses to detect, or even something that isn’t out there in reality somewhere. Imagination is one of the key abilities that make us human. But where did it come from?</p>
<p><a href="https://scholar.google.com/citations?user=Ury0hsMAAAAJ&hl=en&oi=ao">I’m a neuroscientist</a> who studies how children acquire imagination. I’m especially interested in the neurological mechanisms of imagination. Once we identify what brain structures and connections are necessary to mentally construct new objects and scenes, scientists like me can look back over the course of evolution to see when these brain areas emerged – and potentially gave birth to the first kinds of imagination.</p>
<h2>From bacteria to mammals</h2>
<p>After <a href="https://doi.org/10.1038/s41586-019-1436-4">life emerged on Earth</a> around 3.4 billion years ago, organisms gradually became more complex. Around 700 million years ago, neurons organized into <a href="https://doi.org/10.1242/jeb.110692">simple neural nets</a> that then <a href="https://doi.org/10.1101/gr.874803">evolved into the brain and spinal cord</a> around 525 million years ago.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Velociraptor chasing a furry critter" src="https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510737/original/file-20230216-20-wy383x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">It was to mammals’ advantage to hide out while cold-blooded dinosaurs hunted during the day.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/velociraptor-chasing-a-rat-sized-mammal-royalty-free-illustration/168839736">Daniel Eskridge/Stocktrek Images via Getty Images</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1111/j.1469-185X.2009.00094.x">Eventually dinosaurs evolved around 240 million</a> years ago, with <a href="https://doi.org/10.1038/s41586-022-04963-z">mammals emerging a few million years later</a>. While they shared the landscape, dinosaurs were very good at catching and <a href="https://doi.org/10.1080/02724634.2022.2144337">eating small, furry mammals</a>. Dinosaurs were cold-blooded, though, and, like modern cold-blooded reptiles, could only move and hunt effectively <a href="https://doi.org/10.1126/science.1253143">during the daytime when it was warm</a>. To avoid predation by dinosaurs, mammals stumbled upon a solution: <a href="https://doi.org/10.1016/j.ympev.2014.05.016">hide underground during the daytime</a>.</p>
<p>Not much food, though, grows underground. To eat, mammals had to travel above the ground – but the safest time to forage was at night, when dinosaurs were less of a threat. <a href="https://doi.org/10.1038/s41586-022-04963-z">Evolving to be warm-blooded</a> meant mammals could move at night. That solution came with a trade-off, though: Mammals had to eat a lot more food than dinosaurs per unit of weight <a href="https://doi.org/10.1111/brv.12280">in order to maintain their high metabolism</a> and to support their constant inner body temperature around 99 degrees Fahrenheit (37 degrees Celsius).</p>
<p>Our mammalian ancestors had to find <a href="https://doi.org/10.1126/science.1061967">10 times more food</a> during their short waking time, and they had to find it in the dark of night. How did they accomplish this task?</p>
<p>To optimize their foraging, mammals developed a new system to efficiently memorize places where they’d found food: linking the part of the brain that records sensory aspects of the landscape – how a place looks or smells – to the part of the brain that controls navigation. They encoded features of the landscape in the neocortex, the outermost layer of the brain. They encoded navigation in the entorhinal cortex. And the <a href="https://doi.org/10.1038/s41593-018-0189-y">whole system was interconnected</a> by the brain structure called the hippocampus. <a href="https://doi.org/10.1002/hipo.20205">Humans still use this memory system</a> for remembering objects and past events, such as your car and where you parked it.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="two bits of human brain are highlighted, one on each side" src="https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510740/original/file-20230216-14-qjt96p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An interior brain structure called the hippocampus helps synthesize different kinds of information to create memories.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hippocampus-of-the-brain-illustration-royalty-free-illustration/1220616079">Sebastian Kaulitzki/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1016/j.conb.2020.03.014">Groups of neurons</a> in the neocortex encode these memories of objects and past events. Remembering a thing or an episode <a href="https://doi.org/10.1037/a0017937">reactivates the same neurons</a> that initially encoded it. All mammals likely can recall and re-experience previously encoded objects and events by reactivating these groups of neurons. This neocortex-hippocampus-based memory system that evolved 200 million years ago became the first key step toward imagination. </p>
<p>The next building block is the capability to construct a “memory” that hasn’t really happened.</p>
<h2>Involuntary made-up ‘memories’</h2>
<p>The simplest form of imagining new objects and scenes happens in dreams. These vivid, bizarre involuntary fantasies are associated in people with the rapid eye movement (REM) stage of sleep.</p>
<p>Scientists hypothesize that species whose rest includes periods of REM sleep <a href="https://doi.org/10.1038/nrn2716">also experience dreams</a>. Marsupial and placental mammals do have REM sleep, but the egg-laying mammal the echidna does not, suggesting that this stage of the sleep cycle <a href="https://www.worldcat.org/title/317118257">evolved after these evolutionary lines diverged</a> 140 million years ago. In fact, recording from specialized neurons in the brain called <a href="https://doi.org/10.1146/annurev.neuro.31.061307.090723">place cells</a> demonstrated that animals can “dream” of going <a href="https://doi.org/10.7554/eLife.06063">places they’ve never visited before</a>.</p>
<p>In humans, solutions found during dreaming can <a href="https://doi.org/10.1038/nature02223">help solve problems</a>. There are numerous examples of scientific and engineering solutions spontaneously visualized during sleep.</p>
<p>The neuroscientist Otto Loewi dreamed of an experiment that proved nerve impulses are <a href="https://www.nobelprize.org/prizes/medicine/1936/loewi/facts/">transmitted chemically</a>. He immediately went to his lab to perform the experiment – later receiving the Nobel Prize for this discovery.</p>
<p>Elias Howe, the inventor of the first sewing machine, claimed that the main innovation, placing the thread hole near the tip of the needle, <a href="https://dreamsocial.co/famous-dreams-sewing-machine/">came to him in a dream</a>. </p>
<p>Dmitri Mendeleev described seeing in a dream “<a href="https://doi.org/10.1038/35046170">a table where all the elements fell into place as required</a>. Awakening, I immediately wrote it down on a piece of paper.” And that was the periodic table.</p>
<p>These discoveries were enabled by the same mechanism of involuntary imagination first acquired by mammals 140 million years ago.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="young professionals looking at glass wall with post-it notes" src="https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510741/original/file-20230216-14-qmauaf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Intentionally brainstorming ideas depends on being able to control your imagination.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/diverse-businesspeople-smiling-while-having-a-royalty-free-image/1453986826">Goodboy Picture Company/E+ via Getty Images</a></span>
</figcaption>
</figure>
<h2>Imagining on purpose</h2>
<p>The difference between voluntary imagination and involuntary imagination is analogous to the difference between voluntary muscle control and muscle spasm. Voluntary muscle control allows people to deliberately combine muscle movements. Spasm occurs spontaneously and cannot be controlled.</p>
<p>Similarly, voluntary imagination allows people to deliberately combine thoughts. When asked to mentally combine two identical right triangles along their long edges, or hypotenuses, you envision a square. When asked to mentally cut a round pizza by two perpendicular lines, you visualize four identical slices.</p>
<p>This deliberate, responsive and reliable capacity to combine and recombine mental objects is called prefrontal synthesis. It relies on the ability of the prefrontal cortex located at the very front of the brain to control the rest of the neocortex.</p>
<p>When did our species acquire the ability of prefrontal synthesis? Every artifact dated before 70,000 years ago could have been made by a creator who lacked this ability. On the other hand, starting about that time there are various archeological artifacts unambiguously indicating its presence: composite figurative objects, such as <a href="https://doi.org/10.1038/425007a">lion-man</a>; <a href="https://doi.org/10.1016/j.jas.2007.11.006">bone needles with an eye</a>; <a href="https://doi.org/10.1016/j.jas.2011.04.001">bows and arrows</a>; <a href="https://doi.org/10.1016/j.jhevol.2012.03.003">musical instruments</a>; <a href="https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gea.20163">constructed dwellings</a>; <a href="https://doi.org/10.1177/0392192107077649">adorned burials suggesting the beliefs in afterlife</a>, and many more. </p>
<p>Multiple types of archaeological artifacts unambiguously associated with prefrontal synthesis appear simultaneously around 65,000 years ago in multiple geographical locations. This abrupt change in imagination has been characterized by historian Yuval Harari as the “<a href="https://www.penguin.co.uk/books/437186/sapiens-by-yuval-noah-harari/9781784873646">cognitive revolution</a>.” Notably, <a href="https://doi.org/10.1016/j.ajhg.2009.05.001">it approximately coincides with</a> the largest <a href="https://doi.org/10.1086/375120"><em>Homo sapiens</em>‘ migration out of Africa</a>.</p>
<p><a href="https://doi.org/10.1098/rspb.2009.1473">Genetic analyses suggest</a> that a few individuals acquired this prefrontal synthesis ability and then spread their genes far and wide by eliminating other contemporaneous males with the use of an imagination-enabeled strategy and newly developed weapons.</p>
<p>So it’s been a journey of many millions of years of evolution for our species to become equipped with imagination. Most nonhuman mammals have potential for imagining what doesn’t exist or hasn’t happened involuntarily during REM sleep; only humans can voluntarily conjure new objects and events in our minds using prefrontal synthesis.</p><img src="https://counter.theconversation.com/content/190870/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrey Vyshedskiy does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>By learning what parts of the brain are crucial for imagination to work, neuroscientists can look back over hundreds of millions of years of evolution to figure out when it first emerged.Andrey Vyshedskiy, Professor of Neuroscience, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1960162022-12-13T22:56:16Z2022-12-13T22:56:16ZWhy does the Alzheimer’s brain become insulin-resistant?<figure><img src="https://images.theconversation.com/files/499100/original/file-20221205-26-1etuem.jpg?ixlib=rb-1.1.0&rect=7%2C7%2C988%2C555&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Type 2 diabetes, characterised in its advanced stages by insulin resistance, is an important risk factor for Alzheimer's disease.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>As the population ages, the number of people with <a href="https://braininstitute.ca/research-data-sharing/neurodegenerative-disorders">neurodegenerative diseases</a>, such as <a href="https://alzheimer.ca/en/about-dementia/what-alzheimers-disease">Alzheimer’s disease</a>, increases. Approximately <a href="https://www.canada.ca/en/public-health/services/publications/diseases-conditions/dementia-highlights-canadian-chronic-disease-surveillance.html">75,000 Canadians</a> are diagnosed with Alzheimer’s disease each year and experience a decline in their cognitive abilities. The ordeal usually lasts for several years while their family members watch helplessly.</p>
<p>Neurodegenerative diseases are characterized by <a href="https://www.sciencedirect.com/science/article/abs/pii/S0924977X13001107">proteinopathies</a> — abnormal accumulations of proteins in the brain that impair the functioning of <a href="https://cancer.ca/en/cancer-information/resources/glossary/n/neuron">neurons</a>. The most widely studied therapeutic approach to developing drugs for Alzheimer’s is to try to reduce the aggregation of <a href="https://canjhealthtechnol.ca/index.php/cjht/article/view/eh0103/683">amyloid-beta peptide</a> and <a href="https://nouvelles.umontreal.ca/en/article/2022/10/20/unlocking-the-mysteries-of-tauopathies-a-protein-that-gives-hope/">tau protein</a> in neurons.</p>
<p>However, in order to reach their targets, the drugs must first cross the <a href="https://www.theglobeandmail.com/canada/article-toronto-researchers-look-at-new-approach-for-treating-alzheimers/">blood-brain barrier</a> (BBB) from the blood to the brain. This is because <a href="https://www.biorxiv.org/content/10.1101/2020.12.10.419598v1.full">endothelial cells</a>, cells that line the tiniest blood vessels in the brain, regulate the exchange between blood and the brain. They maintain a balance that allows access to essential molecules such as glucose, but restrict the passage of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494002/">most pharmaceuticals</a>, including the new and <a href="https://www.ft.com/content/32478dbf-7270-4eb6-a576-663a47a3603e">much-hyped</a> drug <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2212948">lecanemab</a>.</p>
<p>When these brain endothelial cells become diseased, the balance is upset. The brain struggles to get the substances it needs back into the circulation and rejects those that might harm it.</p>
<p>The brain and the other organs of the body are thus in constant communication, while in health or in disease.</p>
<p>As experts in neurodegenerative diseases and the BBB, we have conducted a study on insulin receptor dysfunction in Alzheimer’s disease.</p>
<h2>Insulin and the brain</h2>
<p><a href="https://www.healthlinkbc.ca/health-topics/types-insulin">Insulin</a> is an essential hormone for life. It is best known for its effect on the regulation of <a href="https://www.diabetescarecommunity.ca/living-well-with-diabetes-articles/blood-sugar-levels-in-canada/?gclid=Cj0KCQiAyracBhDoARIsACGFcS4fee8N8dfBJj9HKxpUiGlNO6RANNF9BiZN52dsd6oxqgLCW7Od_WsaArF9EALw_wcB">blood sugar</a> and remains an essential part of the pharmaceutical treatment of <a href="https://www.healthlinkbc.ca/health-topics/types-insulin">diabetes</a>. In recent decades, researchers have noted vascular and metabolic abnormalities <a href="https://pubmed.ncbi.nlm.nih.gov/30022099/">in a high proportion of patients with dementia</a>.</p>
<p>Indeed, Type 2 diabetes, characterized in the later stages by <a href="http://www.diabetesclinic.ca/en/diab/1basics/insulin_resistance.htm">insulin resistance</a>, is a major risk factor for Alzheimer’s disease. There is some evidence to suggest that the <a href="https://pubmed.ncbi.nlm.nih.gov/29377010/">Alzheimer’s brain is less responsive to insulin</a>. Conversely, studies have shown that insulin can <a href="https://pubmed.ncbi.nlm.nih.gov/32730766/">improve memory</a>, prompting the development of clinical trials on the effect of insulin on Alzheimer’s disease.</p>
<p>Yet we still don’t know what cell types and mechanisms are involved in the action — and loss of action — of insulin in the brain. The vast majority of insulin is produced by the <a href="https://pancreaticcancercanada.ca/the-pancreas/">pancreas</a> and secreted into the bloodstream. Therefore, to affect the brain, insulin must first interact with the BBB and its endothelial cells, which are in contact with the blood and can take up insulin through <a href="https://pubmed.ncbi.nlm.nih.gov/36280236/">receptors</a>.</p>
<h2>Alzheimer’s and the insulin receptor</h2>
<p>In order to measure the amount of these insulin receptors in the brain, <a href="https://doi.org/10.1093/brain/awac309">we performed analyses directly in human tissues</a>. These samples came from a <a href="https://www.rushu.rush.edu/research/departmental-research/religious-orders-study">cohort</a> of over a thousand people who agreed to donate their brains after death. We have access to them through a partnership with researchers at Rush University in Chicago.</p>
<p>We found that the <a href="https://healthenews.mcgill.ca/new-insights-into-how-insulin-interacts-with-its-receptor/">insulin-binding receptor</a> is predominantly located in the microvessels, so, within the BBB itself. Moreover, the abundance of this receptor is decreased in Alzheimer’s patients. This decrease could lead to the loss of insulin response in the Alzheimer brain.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="schematic" src="https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=781&fit=crop&dpr=1 600w, https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=781&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=781&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=982&fit=crop&dpr=1 754w, https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=982&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/499093/original/file-20221205-15238-9izujo.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=982&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The brain insulin receptor is located mainly at the BBB, and its ability to respond to blood insulin is diminished in Alzheimer’s disease.</span>
<span class="attribution"><span class="source">(Manon Leclerc)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Insulin receptor dysfunction</h2>
<p>In order to better control the experimental variables and measure the response of the insulin receptor, we then tested our hypotheses in mice. The <em>in situ</em> cerebral perfusion technique consists of injecting insulin directly into the carotid artery (an artery located in the neck) so that it reaches the brain in its entirety. We have shown that circulating insulin mainly activates receptors located on the cerebral microvessels.</p>
<p>Although it was generally accepted that insulin crosses the BBB to reach cells such as neurons deeper in the brain tissue, our results show that the proportion of insulin that crosses the BBB is low.</p>
<p>These two observations thus confirm that the majority of insulin must interact with cells in the BBB before it can exert an action on the brain.</p>
<p>We then applied the same method to <a href="https://www.criver.com/products-services/research-models-services/genetically-engineered-model-services/transgenic-mouse-rat-model-creation/transgenic-mice?region=3601">transgenic mice</a>, which were genetically modified to model Alzheimer’s disease. We found that the response to insulin at the BBB was dysfunctional, with no activation of the insulin receptor in these diseased mice.</p>
<p>Thus, in both humans and rodents, the brain insulin receptor is located primarily at the BBB, and its ability to respond to blood insulin is impaired in Alzheimer’s disease.</p>
<h2>A significant breakthrough</h2>
<p>In sum, our results suggest that alterations in the number, structure and function of insulin receptors at the level of BBB endothelial cells may contribute to the cerebral insulin resistance observed in Alzheimer’s disease.</p>
<p>Alzheimer’s research efforts are currently focused on drugs that, in order to reach their therapeutic target, the neurons, must first cross the BBB, which severely restricts their passage. By targeting the metabolic dysfunction of the brain instead, we propose a research alternative that has two major advantages.</p>
<p>The first is that we can use treatments that do not have to cross the BBB barrier, since it is the endothelial cells themselves that become the therapeutic target. The second involves <a href="https://www.nature.com/articles/nrd.2018.168">“drug repurposing,”</a> which consists of taking advantage of the phenomenal therapeutic arsenal already approved to fight diabetes and obesity, but using this in the context of Alzheimer’s.</p>
<p>It should be remembered that the few drugs available to us provide only a modest improvement in symptoms. Combating insulin resistance in the brain would make it possible to break the vicious circle between neuropathology (disease that affects the brain) and diabetes, and in theory slow down the progression of the disease.</p>
<h2>The work is not finished</h2>
<p>On the basic research side, we will continue to study the mechanisms downstream from the microvessels to understand the action of insulin on the deep layers of the brain.</p>
<p>We hope that clinical research will follow suit with human studies to repurpose drugs that target certain metabolic diseases, such as diabetes, towards fighting Alzheimer’s.</p>
<p>In the meantime, while waiting for pharmaceutical solutions, each of us would do well to adopt the preventive cocktail that we all know well: a healthy diet combined with frequent physical and mental exercise.</p><img src="https://counter.theconversation.com/content/196016/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Frederic Calon has received funding from: Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Fonds de la recherche du Québec en santé (FRQS), Alzheimer Society of Canada.</span></em></p><p class="fine-print"><em><span>Manon Leclerc has received scholarships from the Fondation du CHU de Québec and the Fonds de Recherche du Québec - Santé (FRQS).</span></em></p><p class="fine-print"><em><span>Vincent Emond ne travaille pas, ne conseille pas, ne possède pas de parts, ne reçoit pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'a déclaré aucune autre affiliation que son organisme de recherche.</span></em></p>Impaired insulin receptors in the blood vessels between the blood and the brain may contribute to the insulin resistance observed in Alzheimer’s disease.Frederic Calon, Professeur, Université LavalManon Leclerc, PhD student, Université LavalVincent Emond, Professionnel de recherche, Université LavalLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1938192022-11-07T12:34:36Z2022-11-07T12:34:36ZEpilepsy: gene therapy technique targeting overactive brain cells shows promise in treating drug-resistant form of the condition<figure><img src="https://images.theconversation.com/files/493789/original/file-20221107-13-i4n7qr.jpg?ixlib=rb-1.1.0&rect=26%2C0%2C3500%2C1996&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epileptic seizures are caused by brain cells becoming overactive.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/neuronal-network-electrical-activity-neuron-cells-1691666992">MattLphotography/ Shutterstock</a></span></figcaption></figure><p>Something like <a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy">50 million people worldwide</a> have epilepsy. While the majority of these people are able to use medications to manage and prevent their seizures, around one-third don’t respond well to these treatments. In such cases, the only option available to bring seizures under control is to <a href="https://epilepsysociety.org.uk/about-epilepsy/treatment/epilepsy-and-brain-surgery">remove the part of the brain</a> where seizures arise. But this procedure is extremely risky.</p>
<p>Since epileptic seizures are caused by excessive activity of brain cells (neurons) in specific parts of the brain, being able to target these neurons and turn them off could very well prevent seizures from happening.</p>
<p>Using an innovative new gene therapy approach we have developed, we were able to show in cell and animal models that it is possible to <a href="https://www.science.org/doi/epdf/10.1126/science.abq6656">specifically target the neurons</a> that cause epileptic seizures. This subsequently prevented them from becoming overactive and causing seizures in the future. </p>
<p>This discovery not only has major implications for treating drug-resistant epilepsy, but there’s a chance it may also be used to treat other neurological conditions caused by overactive neurons, including Parkinson’s disease and migraines.</p>
<h2>Gene therapy</h2>
<p>Gene therapy works by directly altering a person’s genes in order to treat a disease or condition. There are a few different ways of doing this.</p>
<p><a href="https://www.jneurosci.org/content/early/2019/02/12/JNEUROSCI.1143-18.2019?versioned=true">Previous studies</a> that have used gene therapy to treat epilepsy in animal models have done this by using a virus that has been altered in the lab so it’s no longer harmful. Researchers would inject the virus into the brain region where seizures occur. The virus would then implant stretches of DNA into the cells, effectively modulating the way they worked – <a href="https://www.nature.com/articles/s41591-018-0103-x">making them less active</a> and preventing seizures.</p>
<p>While this technique is far less invasive than brain surgery, the problem with the method is that it affects all the neurons in the brain region – not just those causing the seizures. It also permanently alters the properties of the cells that take up the virally delivered DNA, which can permanently modify brain function. </p>
<p>But our innovative new gene therapy tool has shown it’s possible to alter only the brain cells that cause seizures, leaving nearby healthy neurons unaffected. We were able to do this by taking advantage of how gene expression is normally regulated.</p>
<figure class="align-center ">
<img alt="An image of multiple DNA strands." src="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our new gene therapy tool targeted the body’s promoters.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dna-molecule-macro-blue-string-on-775854724">SynthEx/ Shutterstock</a></span>
</figcaption>
</figure>
<h2>The role of promoters</h2>
<p>The 20,000 or so genes we have in our body each contain instructions to make different proteins and molecules. These genes are typically under the control of neighbouring stretches of DNA, called promoters. These determine whether and how much of a particular protein is made. Different cells express different proteins depending on which promoters are active or inactive.</p>
<p>There’s also a special type of promoter (called “activity-dependent” promoters) that will only switch on in response to biochemical signals made by neurons when they fire intensely – such as during a seizure. We took advantage of these activity-dependent promoters, creating a gene therapy that senses and turns down the excitability of neurons that cause seizures. We did this by coupling activity-dependent promoters to DNA sequences that contain proteins which calm down neurons.</p>
<p>We initially tested the gene therapy tool in neurons grown in a dish, and then in mice that had drug-resistant epilepsy. We also tested this technique in lab-grown human “mini brains”. </p>
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Read more:
<a href="https://theconversation.com/scientists-grow-brain-tissue-with-different-regions-in-lab-17560">Scientists grow brain tissue with different regions in lab</a>
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<p>In each test, we were able to show this new gene therapy technique was effective in calming down the overactive neurons involved in seizures, while leaving healthy bystander cells unaffected.</p>
<p>Although it takes an hour or so to switch on – longer than the typical duration of a seizure – the new gene therapy is highly effective in preventing subsequent seizures. It does this by automatically selecting which neurons to treat and switching them off. It’s also able to return neurons to their original state when brain activity returns to normal. If seizures occur again, the promoter is ready to switch on. </p>
<p>The treatment therefore only has to be given once, but has a lasting effect – possibly lifelong. Importantly, the treatment did not affect the performance of the mice in tests of memory and other normal behaviour (such as their anxiety levels, learning and mobility).</p>
<p>We are excited by the breakthrough, because it could in principle bring the prospect of gene therapy to a wide range of people with drug-resistant epilepsy. But before the therapy is ready to use with these patients, we will need to put it through a number of tests to verify that it can be scaled up to larger brains.</p><img src="https://counter.theconversation.com/content/193819/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gabriele Lignani consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from Epilepsy Research UK and Medical Research Council. </span></em></p><p class="fine-print"><em><span>Dimitri Kullmann consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from the Wellcome Trust and the Medical Research Council.</span></em></p>This technique could also be applied to other conditions, such as Parkinson’s disease.Gabriele Lignani, Associate Professor, Clinical & Experimental Epilepsy, UCLDimitri Kullmann, Professor of Neurology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1895192022-09-01T18:04:30Z2022-09-01T18:04:30ZAxolotls can regenerate their brains – these adorable salamanders are helping unlock the mysteries of brain evolution and regeneration<figure><img src="https://images.theconversation.com/files/482164/original/file-20220831-8166-9xe77t.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4096%2C2728&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Axolotls are a model organism researchers use to study a variety of topics in biology.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/aE4bnU">Ruben Undheim/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The <a href="https://www.nationalgeographic.com/animals/amphibians/facts/axolotl">axolotl</a> (<em>Ambystoma mexicanum</em>) is an aquatic salamander renowned for its ability to <a href="https://doi.org/10.1159%2F000504294">regenerate its spinal cord, heart and limbs</a>. These amphibians also <a href="https://doi.org/10.1186/1749-8104-8-1">readily make new neurons</a> throughout their lives. In 1964, researchers observed that adult axolotls could <a href="https://pubmed.ncbi.nlm.nih.gov/14248567/">regenerate parts of their brains</a>, even if a large section was completely removed. But one study found that axolotl <a href="https://doi.org/10.7554/eLife.13998">brain regeneration</a> has a limited ability to rebuild original tissue structure.</p>
<p>So how perfectly can axolotl’s regenerate their brains after injury? </p>
<p>As a <a href="https://scholar.google.com/citations?user=OdA08uIAAAAJ&hl=en">researcher studying regeneration at the cellular level</a>, I and my colleagues in the <a href="https://bsse.ethz.ch/qdb">Treutlein Lab</a> at ETH Zurich and the <a href="http://tanakalab.org">Tanaka Lab</a> at the Institute of Molecular Pathology in Vienna wondered whether axolotls are able to regenerate all the different cell types in their brain, including the connections linking one brain region to another. In our <a href="https://science.org/doi/10.1126/science.abp9262">recently published study</a>, we created an atlas of the cells that make up a part of the axolotl brain, shedding light on both the way it regenerates and brain evolution across species.</p>
<h2>Why look at cells?</h2>
<p>Different <a href="https://doi.org/10.1038/nrg2416">cell types</a> have different functions. They are able to specialize in certain roles because they each express different genes. Understanding what types of cells are in the brain and what they do helps clarify the overall picture of how the brain works. It also allows researchers to make comparisons across evolution and try to find biological trends across species.</p>
<p>One way to understand which cells are expressing which genes is by using a technique called <a href="https://doi.org/10.3389/fgene.2019.00317">single-cell RNA sequencing (scRNA-seq)</a>. This tool allows researchers to count the number of active genes within each cell of a particular sample. This provides a “snapshot” of the activities each cell was doing when it was collected. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/k9VFNLLQP8c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Single-cell RNA sequencing can provide information on the specific function of each cell in a sample.</span></figcaption>
</figure>
<p>This tool has been instrumental in understanding the types of cells that exist in the brains of animals. Scientists have used scRNA-seq in <a href="https://doi.org/10.1038%2Fnbt.4103">fish</a>, <a href="https://doi.org/10.1126/science.aar4237">reptiles</a>, <a href="https://doi.org/10.1016/j.cell.2018.06.021">mice</a> and even <a href="https://doi.org/10.1126/science.aap8809">humans</a>. But one major piece of the brain evolution puzzle has been missing: amphibians.</p>
<h2>Mapping the axolotl brain</h2>
<p>Our team decided to focus on the <a href="https://doi.org/10.1016/B978-0-323-39632-5.00016-5">telencephalon</a> of the axolotl. In humans, the telencephalon is the largest division of the brain and contains a region called the <a href="https://doi.org/10.1038/nrn2719">neocortex</a>, which plays a key role in animal behavior and cognition. Throughout recent evolution, the neocortex has <a href="https://doi.org/10.3389/fnana.2014.00015">massively grown in size</a> compared with other brain regions. Similarly, the types of cells that make up the telencephalon overall have <a href="https://doi.org/10.1016/j.pneurobio.2020.101865">highly diversified</a> and grown in complexity over time, making this region an intriguing area to study.</p>
<p>We used scRNA-seq to identify the different types of cells that make up the axolotl telencephalon, including different types of <a href="https://www.ninds.nih.gov/health-information/patient-caregiver-education/brain-basics-life-and-death-neuron">neurons</a> and <a href="https://doi.org/10.3389/fnana.2018.00104">progenitor cells</a>, or cells that can divide into more of themselves or turn into other cell types. We identified what genes are active when <a href="https://doi.org/10.3389/fcell.2020.00533">progenitor cells become neurons</a>, and found that many pass through an intermediate cell type called neuroblasts – previously unknown to exist in axolotls – before becoming mature neurons.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/uooR4293p_4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Axolotls’ regenerative abilities have been a source of fascination for scientists.</span></figcaption>
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<p>We then put axolotl regeneration to the test by removing one section of their telencephalon. Using a <a href="https://doi.org/10.1126/science.aad7038">specialized method of scRNA-seq</a>, we were able to capture and sequence all the new cells at different stages of regeneration, from one to 12 weeks after injury. Ultimately, we found that all cell types that were removed had been completely restored.</p>
<p>We observed that brain regeneration happens in three main phases. The first phase starts with a rapid increase in the number of progenitor cells, and a small fraction of these cells activate a wound-healing process. In phase two, progenitor cells begin to differentiate into neuroblasts. Finally, in phase three, the neuroblasts differentiate into the same types of neurons that were originally lost.</p>
<p>Astonishingly, we also observed that the severed <a href="https://www.brainfacts.org/thinking-sensing-and-behaving/brain-development/2012/making-connections">neuronal connections</a> between the removed area and other areas of the brain had been reconnected. This rewiring indicates that the regenerated area had also regained its original function.</p>
<h2>Amphibians and human brains</h2>
<p>Adding amphibians to the evolutionary puzzle allows researchers to infer how the brain and its cell types has changed over time, as well as the mechanisms behind regeneration.</p>
<p>When we compared our axolotl data with other species, we found that cells in their telencephalon show strong similarity to the mammalian <a href="https://www.ncbi.nlm.nih.gov/books/NBK482171/">hippocampus</a>, the region of the brain involved in memory formation, and the <a href="https://doi.org/10.1016/B978-0-12-801238-3.04706-1">olfactory cortex</a>, the region of the brain involved in the sense of smell. We even found some similarities in one axolotl cell type to the neocortex, the area of the brain known for perception, thought and spatial reasoning in humans. These similarities indicate that these areas of the brain may be evolutionarily conserved, or stayed comparable over the course of evolution, and that the neocortex of mammals may have an ancestor cell type in the telencephalon of amphibians.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Axolotl in tank" src="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482165/original/file-20220831-4904-pdq0jw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Cracking the mystery of axolotl regeneration could lead to improvements in medical treatments for severe injuries.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Axolotl_ambystoma_mexicanum_anfibio_ASAG.jpg">Amandasofiarana/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>While our study sheds light on the process of brain regeneration, including which genes are involved and how cells ultimately become neurons, we still don’t know what <a href="https://www.nature.com/scitable/topicpage/cell-signaling-14047077/">external signals</a> initiate this process. Moreover, we don’t know if the processes we identified are still accessible to animals that evolved later in time, such as mice or humans.</p>
<p>But we’re not solving the brain evolution puzzle alone. The <a href="https://www.tosches-lab.com/">Tosches Lab</a> at Columbia University explored the diversity of cell types in <a href="https://science.org/doi/10.1126/science.abp9186">another species of salamander, <em>Pleurodeles waltl</em></a>, while the Fei lab at the Guangdong Academy of Medical Sciences in China and collaborators at life sciences company <a href="https://en.genomics.cn/">BGI</a> explored how cell types are <a href="https://science.org/doi/10.1126/science.abp9444">spatially arranged in the axolotl forebrain</a>.</p>
<p>Identifying all the cell types in the axolotl brain also helps pave the way for innovative research in regenerative medicine. The brains of mice and humans have <a href="https://doi.org/10.1100/tsw.2011.113">largely lost their capacity</a> to repair or regenerate themselves. <a href="https://doi.org/10.4103%2F1673-5374.270294">Medical interventions</a> for severe brain injury currently focus on drug and stem cell therapies to boost or promote repair. Examining the genes and cell types that allow axolotls to accomplish nearly perfect regeneration may be the key to improve treatments for severe injuries and unlock regeneration potential in humans.</p><img src="https://counter.theconversation.com/content/189519/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashley Maynard works at ETH Zurich and has disclosed no relevant affiliations beyond her academic appointment.</span></em></p>Axolotls are amphibians known for their ability to regrow their organs, including their brains. New research clarifies their regeneration process.Ashley Maynard, PhD Candidate in Quantitative Developmental Biology, Swiss Federal Institute of Technology ZurichLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1876072022-08-04T12:22:28Z2022-08-04T12:22:28ZIlluminating the brain one neuron and synapse at a time – 5 essential reads about how researchers are using new tools to map its structure and function<figure><img src="https://images.theconversation.com/files/475765/original/file-20220725-30588-3lzyhd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1960%2C1527&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The U.S. BRAIN Initiative seeks to elucidate the connection between brain structure and function.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/computer-artwork-of-human-brain-profile-royalty-free-illustration/85757401">Science Photo Library - PASIEKA/Brand X Pictures via Getty Images</a></span></figcaption></figure><p>Scientists know both a lot and very little about the brain. With <a href="https://doi.org/10.48550/arXiv.1906.01703">billions of neurons and trillions of connections</a> among them, and the experimental limitations of examining the seat of consciousness and bodily function, studying the human brain is a technical, theoretical and ethical challenge. And one of the biggest challenges is perhaps one of the most fundamental – seeing what it looks like in action.</p>
<p>The U.S. <a href="https://braininitiative.nih.gov">Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative</a> is a collaboration among the National Institutes of Health, Defense Advanced Research Projects Agency, National Science Foundation, Food and Drug Administration and Intelligence Advanced Research Projects Activity and others. Since its inception in 2013, <a href="https://braininitiative.nih.gov">its goal</a> has been to develop and use new technologies to examine how each neuron and neural circuit comes together to “record, process, utilize, store, and retrieve vast quantities of information, all at the speed of thought.”</p>
<p>Just as <a href="https://theconversation.com/genomic-sequencing-heres-how-researchers-identify-omicron-and-other-covid-19-variants-172935">genomic sequencing</a> enabled the creation of a <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">comprehensive map of the human genome</a>, tools that elucidate the connection between brain structure and function could help researchers answer long-standing questions about how the brain works, both in sickness and in health.</p>
<p>These five stories from our archives cover research that has been funded by or advances the goals of the BRAIN Initiative, detailing a slice of what’s next in neuroscience.</p>
<h2>1. Mapping the brain</h2>
<p>Attempts to map the structure of the brain date back to <a href="https://web.stanford.edu/class/history13/earlysciencelab/body/brainpages/brain.html">antiquity</a>, when philosophers and scholars had only the unaided eye to map anatomy to function. New <a href="https://embryo.asu.edu/pages/golgi-staining-technique">visualization techniques</a> in the 20th century led to the discovery that, just like all the other organs of the body, the brain is composed of individual cells – <a href="https://doi.org/10.1016/j.cub.2006.02.053">neurons</a>.</p>
<p>Now, <a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">further advances in microscopy</a> that make use of artificial intelligence and genomics have allowed scientists not just to see each individual neuron in the entire brain, but also to identify the connections among them and begin to ascertain their function. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Stitched high-resolution microscopy image of mouse brain." src="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Zooming in on this high-resolution image of a mouse brain reveals rectangular lines where individual image tiles were stitched together, each colored dot representing a specific cell type.</span>
<span class="attribution"><a class="source" href="http://kimlab.io">Yongsoo Kim</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Neuroscientist <a href="https://scholar.google.com/citations?user=WOQx1ksAAAAJ&hl=en">Yongsoo Kim</a> of Penn State likened this method to a photo mosaic, piecing together areas of the brain that haven’t been charted before. “It’s like building a Google map of the brain,” wrote Kim. “By combining millions of individual street photos, you can zoom in to see each street corner and zoom out to see an entire city.” Creating these high-resolution maps, he wrote, could help scientists develop new theories on how the brain works and lead to better treatments for brain disorders like dementia.</p>
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Read more:
<a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">Mapping how the 100 billion cells in the brain all fit together is the brave new world of neuroscience</a>
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<h2>2. Brain folds and wrinkles</h2>
<p>Another fundamental question researchers have been puzzling over is how the brain develops the bumps and grooves that riddle its surface. Until roughly the <a href="https://doi.org/10.1093%2Fcercor%2Fbhr053">second trimester</a> of fetal development, the human brain is completely smooth.</p>
<p>Scientists have proposed a number of theories on the mechanics of brain folding. One of them, <a href="https://www.jstor.org/stable/1740783">differential tangential growth</a>, posits that folds form because of a mismatch in growth rates between the outer and inner layers of the brain. To ease the forces compressing the outer layer and restore structural stability, the layers buckle and fold.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/WBWJBFRnqwY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Harvard researchers modeled how folding reduces instability caused by differential growth rates in the brain.</span></figcaption>
</figure>
<p>Biomechanical engineer <a href="https://scholar.google.com/citations?user=ukOZ0BAAAAAJ&hl=en">Mir Jalil Razavi</a> and computer scientist <a href="https://scholar.google.com/citations?user=r6DIjzUAAAAJ&hl=en">Weiying Dai</a> of Binghamton University <a href="https://theconversation.com/brain-wrinkles-and-folds-matter-researchers-are-studying-the-mechanics-of-how-they-form-170194">created models</a> to clarify this theory. They identified other factors that may also be at play, like the number of axons – the part of the neuron that transmits electrical signals – in a particular area. “Our brain models provide a potential explanation for why brains may form abnormally during development, highlighting the important role that the brain’s structure plays in its proper functioning,” they wrote.</p>
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Read more:
<a href="https://theconversation.com/brain-wrinkles-and-folds-matter-researchers-are-studying-the-mechanics-of-how-they-form-170194">Brain wrinkles and folds matter – researchers are studying the mechanics of how they form</a>
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<h2>3. Where memories are stored</h2>
<p>Just like the RAM in a computer, memories take up physical space in the brain. Researchers have hypothesized that memories may be stored by <a href="https://doi.org/10.1016/0166-2236(94)90101-5">rearranging the connections, or synapses</a>, among neurons. While this theory has largely been confirmed by observing <a href="https://doi.org/10.1038/37601">changes in the electrical signals</a> neurons produce after memory formation, what triggers these changes has been unclear.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Image of magenta-colored neurons in a live fish brain, with the synapses colored in green" src="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=766&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=766&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=766&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=963&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=963&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=963&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Neurons in a live fish brain, with synapses colored green.</span>
<span class="attribution"><span class="source">Zhuowei Du and Don B. Arnold</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
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<p>Biomedical engineer <a href="https://scholar.google.com/citations?user=z040dHgAAAAJ&hl=en">Don Arnold</a> of the University of Southern California and his colleagues took a mapping approach. They <a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">compared 3D maps of zebrafish synapses</a> before and after memory formation – namely, learning to associate a light with an unpleasant stimulus. They found that one brain region gained synapses while another’s were destroyed, indicating that associative memories may be a result of the formation and loss of connections among neurons.</p>
<p>These findings imply that it might one day be possible to treat conditions like PTSD by physically erasing the associative memory linking a harmless trigger with a traumatic experience. More research is needed, and there are obvious ethical considerations to address. “Nevertheless,” Arnold wrote, “it’s tempting to imagine a distant future in which synaptic surgery could remove bad memories.”</p>
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Read more:
<a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">Where are memories stored in the brain? New research suggests they may be in the connections between your brain cells</a>
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<h2>4. Seizures hijack memory pathways</h2>
<p><a href="https://www.epilepsy.com/what-is-epilepsy/understanding-seizures">Seizures</a> are sudden surges of electrical activity in the brain. People who experience temporal lobe seizures are sometimes unable to remember what happened immediately prior. This may be due to disruptions to the circuitry in the hippocampus, the part of the temporal lobe key to memory consolidation.</p>
<p>Neurology researchers <a href="https://scholar.google.com/citations?user=bjrXv58AAAAJ&hl=en&oi=ao">Anastasia Brodovskaya</a> and <a href="https://scholar.google.com/citations?user=nMb-pTcAAAAJ&hl=en">Jaideep Kapur</a> of the University of Virginia hypothesized that seizures can cause memory loss by <a href="https://theconversation.com/seizures-can-cause-memory-loss-and-brain-mapping-research-suggests-one-reason-why-172280">using the same pathways</a> the brain uses to process memories. They mapped the neurons of mice learning to navigate a maze and during induced seizures, finding that both cases activated the same brain circuits.</p>
<p>“Because they use the same brain pathways, seizures can disrupt the memory consolidation process by taking over the circuit,” they wrote. “This meant that seizures can hijack the memory pathways and cause amnesia.”</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/seizures-can-cause-memory-loss-and-brain-mapping-research-suggests-one-reason-why-172280">Seizures can cause memory loss, and brain-mapping research suggests one reason why</a>
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</p>
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<h2>5. What the nose knows</h2>
<p>What the eye can’t see, the nose can for many organisms. From dogs to mosquitoes, many animals behave in ways that allow them to detect and pursue an odor long before its source comes into view.</p>
<p>Scientists <a href="https://scholar.google.com/citations?user=wn_f7y0AAAAJ&hl=en">John Crimaldi</a>, <a href="https://scholar.google.com/citations?user=JEi-fdoAAAAJ&hl=en">Brian Smith</a>, <a href="https://www.bbe.caltech.edu/people/elizabeth-j-hong">Elizabeth Hong</a> and <a href="https://scholar.google.com/citations?user=GpkJjVUAAAAJ&hl=en">Nathan Urban</a> of the <a href="https://www.odor2action.org/">Odor2Action</a> research network use technology to study olfaction, or sense of smell. They <a href="https://theconversation.com/from-odor-to-action-how-smells-are-processed-in-the-brain-and-influence-behavior-173811">trace how the shape of an odor plume</a> informs how it will be detected, how those odor molecules are translated into electrical signals in the brain, and how these electrical signals are reformatted into useful information that influence behavior.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/MyHR6a-zJM0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video from the Wachowiak Lab at the University of Utah shows the activity of the olfactory bulb in a mouse brain. Each odor the mouse is exposed to makes different combinations of neurons light up.</span></figcaption>
</figure>
<p>A better understanding of the olfactory system, they wrote, can lead to the development of <a href="https://doi.org/10.1177%2F0278364908095118">electronic noses</a> that make searching for chemical weapons and disaster victims safer for people and animals. They also believe that examining the olfactory system can help advance study of the brain. “Its relative simplicity is what allows scientists like us to study it from end to end and learn how the brain works as a whole,” they wrote.</p>
<p>While a grand unified theory of the brain still remains elusive, new tools and techniques are helping researchers excavate its hidden depths. As Crimaldi and his team put it, “An exciting future in scientific and medical development, we believe, is right under our noses.”</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/from-odor-to-action-how-smells-are-processed-in-the-brain-and-influence-behavior-173811">From odor to action – how smells are processed in the brain and influence behavior</a>
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<p><em>Editor’s note: This story is a roundup of articles from The Conversation’s archives.</em></p><img src="https://counter.theconversation.com/content/187607/count.gif" alt="The Conversation" width="1" height="1" />
From figuring out where memories are stored to how sensory information translates to behavior, new technologies are helping neuroscientists better understand how the brain works.Vivian Lam, Associate Health and Biomedicine EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847242022-08-02T16:11:03Z2022-08-02T16:11:03ZWhat epilepsy teaches us about diversity and resilience<figure><img src="https://images.theconversation.com/files/476338/original/file-20220727-1405-kljymn.jpg?ixlib=rb-1.1.0&rect=26%2C33%2C4466%2C2957&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epilepsy is characterized by spontaneous and recurrent seizures, often triggered by stress or visual stimuli.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>There is a growing recognition of the importance of equity, diversity and inclusion in society and its institutions. The most progressive, leading-edge organizations consider the diversity of people to be <a href="https://www.canada.ca/en/treasury-board-secretariat/corporate/reports/building-diverse-inclusive-public-service-final-report-joint-union-management-task-force-diversity-inclusion.html">essential to the success, growth, innovation and development of a society</a>.</p>
<p>The benefits of diversity, however, are far from exclusive to human organizations; heterogeneity and variability are design principles central to all complex natural systems, whether they are <a href="https://doi.org/10.1155/2018/3421529">ecological, cellular or genetic networks</a>.</p>
<p>Whether we are talking about an ecosystem, society or the brain, how does this diversity relate to the functioning and stability of a complex system?</p>
<p>As neuroscientists, our interdisciplinary research and clinical work has drawn us to the incredible complexity and richness of the human brain and natural systems. We seek not only to better understand how the brain’s circuitry works, but also to develop new treatments for neurological diseases such as epilepsy.</p>
<h2>Diversity means resilience</h2>
<p><a href="https://tile.loc.gov/storage-services/service/rbc/rbctos/2017gen17473/2017gen17473.pdf">First developed by Darwin</a>, the idea that diversity leads to stability and survival has been <a href="https://www.hindawi.com/journals/complexity/2018/3421529/">debated by scientists from many disciplines for over a century</a>. The ability of natural systems to resist change is a characteristic known as resilience. This fundamental characteristic emerges from interactions between members of the same system — such as species in an ecosystem, individuals in a group or cells in an organism — and enables it to maintain its functions over time.</p>
<p>Resilience is tested by change. Some ecosystems can adapt to the extinction of specific species or to drought. Some virtual communities or social networks can withstand cyberattacks. Some organizations can continue to operate in the wake of conflict, war, political revolution or … pandemic. </p>
<p>In light of these common examples — and many others related to the social or natural sciences — it is now more important than ever to understand the role played by diversity in maintaining the resilience of complex systems.</p>
<p>What if clues to the answer lie in the circuits of the brain, specifically in a brain with epilepsy?</p>
<h2>Tipping over in an electrical storm</h2>
<p>For several years, our interdisciplinary team has been studying epilepsy, <a href="https://doi.org/10.1046/j.1528-1157.43.s.6.1.x">the most common severe neurological disorder</a>. Epilepsy is characterized primarily by the apparently spontaneous and recurrent occurrence of seizures, often triggered by stress or visual stimuli (<a href="https://doi.org/10.1016/j.cub.2017.03.067">such as flashing lights or specific images</a>). Recent research has also shown that <a href="https://doi.org/10.1038/s41467-017-02577-y">the frequency of these seizures can vary with the time of day or month</a>, depending on the individual’s sleep-wake cycle, for example.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="woman holding herself against a wall with one hand and her head with the other while she appears to be having a seizure" src="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Epilepsy is the most common serious neurological disorder.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>In this light, a brain with epilepsy can be seen as fragile and not resilient, regularly tipping into an electrical storm. Thus, rather than adapting normally to changes, neurons become disproportionately active and synchronous, and the resulting intense electrical activity spreads, disrupting brain function.</p>
<p>Because of the significant impact of these seizures on patients and their families, our team has been relentlessly studying the circuits responsible for triggering them and exploring ways to prevent them.</p>
<p>What does diversity have to do with epilepsy? Our team recently measured the activity of neurons in people with epilepsy. We found that neurons in the brain regions responsible for triggering seizures <a href="https://doi.org/10.1016/j.celrep.2022.110863">were much less diverse than those in regions not responsible for seizures</a>. These neurons were strangely similar to each other, showing highly similar characteristics and responses.</p>
<p>Could this lack of diversity explain why seizure-prone brains are less resilient?</p>
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<h2>Mathematical models to the rescue</h2>
<p>To answer this complex question, we turned to mathematics. What if, through mathematical models of brain circuitry, we could understand how neural diversity (or the lack thereof) predicts seizure resilience? Could we determine whether neuronal diversity promotes resilience in the brain?</p>
<p>Using our equations, we found that when diversity was too low, seizure-like activity would spontaneously emerge: <a href="https://doi.org/10.1016/j.celrep.2022.110863">the activity of the neurons would become vulnerable to sudden change in synchrony</a>, reminiscent of what we observe during seizures. These results are unequivocal: low diversity made these neuronal circuits fragile, poorly resilient and unable to maintain the type of activity required to preserve brain function.</p>
<p>What do these result mean? They provide key insights about the role played by different types of neurons in maintaining brain function. </p>
<p>These results are helping us look at neurological diseases such as epilepsy differently than we did before, potentially opening up new avenues on how to treat them. Our approach of using interdisciplinary methods and mathematics allows us to go further and understand better how diversity increases resilience, providing invaluable cues and answering hard questions such as: Is there an optimal level of diversity? What are the different types of diversities and do they all promote stability equally? Could we enhance resilience by promoting neuronal diversity through targeted therapeutic interventions?</p>
<p>Most importantly, our results also provide a powerful reminder of the primordial role diversity plays in the robustness of systems in the face of change: which holds true not only for neurons and circuits, but for humans and collectives as well. Variety truly is the spice of life.</p><img src="https://counter.theconversation.com/content/184724/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jérémie Lefebvre has received funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR).</span></em></p><p class="fine-print"><em><span>Taufik A. Valiante has received funding from the Krembil Brain Institute, and the Natural Sciences and Engineering Research Council of Canada (NSERC).</span></em></p>Our team studied the activity of neurons in people with epilepsy. Neurons in the brain regions responsible for triggering seizures were much less diverse.Jérémie Lefebvre, Professeur agrégé de neurosciences computationnelles et neurophysiologie, L’Université d’Ottawa/University of OttawaTaufik A. Valiante, Neurosurgeon/neuroscientist, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1872852022-07-20T03:05:52Z2022-07-20T03:05:52ZGame of Thrones star Emilia Clarke is missing ‘quite a bit’ of her brain. How can people survive and thrive after brain injury?<p>In a recent <a href="https://www.bbc.co.uk/iplayer/episode/m0019f3z/sunday-morning-17072022">interview</a>, Game of Thrones star Emilia Clarke spoke about being able to live “completely normally” after two aneurysms – one in <a href="https://www.newyorker.com/culture/personal-history/emilia-clarke-a-battle-for-my-life-brain-aneurysm-surgery-game-of-thrones">2011 and one in 2013</a> – that caused brain injury. She went on to have two brain surgeries.</p>
<p>An aneurysm is a bulge or ballooning in the wall of a blood vessel, often accompanied by severe headache or pain. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1548671018499194883"}"></div></p>
<p>So how can people survive and thrive despite having, as Clarke <a href="https://www.marieclaire.com.au/emilia-clarke-aneurysm">put</a> it, “quite a bit missing” from their brain?</p>
<p>The key to understanding how brains can recover from trauma is that they are fantastically plastic – meaning our body’s supercomputer can reshape and remodel itself.</p>
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<strong>
Read more:
<a href="https://theconversation.com/growing-up-in-a-disadvantaged-neighbourhood-can-change-kids-brains-and-their-reactions-184145">Growing up in a disadvantaged neighbourhood can change kids' brains – and their reactions</a>
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<h2>Our fantastically plastic brains</h2>
<p>Brains can adapt and change in incredible ways. Yours is doing it right now as you form new memories. </p>
<p>It’s not that the brain has evolved to deal with brain trauma or stroke or aneurysms; our ancestors normally died when that happened and may not have gone on to reproduce. In fact, we evolved very thick skulls to try to prevent brain trauma happening at all.</p>
<p>No, this <a href="https://www.frontiersin.org/articles/10.3389/fncel.2019.00066/full">neural plasticity</a> is a result of our brains evolving to be learning machines. They allow us to adapt to changing environments, to facilitate learning, memory and flexibility. This functionality also means the brain can adapt after certain injuries, finding new pathways to function.</p>
<p>A lot of organs wouldn’t recover at all after serious damage. But the brain keeps developing through life. At a microscopic level, you’re changing the brain to make new memories every day.</p>
<p>This extraordinary kilogram and a half of soft tissue sitting in your skull – with more power and capacity than even the most powerful supercomputer – has an incredible ability to adapt.</p>
<h2>What does it mean to say parts of the brain are ‘missing’?</h2>
<p>The brain needs a constant and steady <a href="https://www.urmc.rochester.edu/news/story/study-reveals-brains-finely-tuned-system-of-energy-supply#:%7E:text=In%20fact%2C%20the%20brain's%20oxygen,brain%20activity%20and%20blood%20flow.">supply</a> of oxygenated blood. When it is injured – for example by an aneurysm, sudden impact against the inside of the skull, stroke or surgery – oxygen supply can be interrupted. </p>
<p>Sometimes, a piece is surgically <a href="https://www.wired.com/story/she-was-missing-a-chunk-of-her-brain-it-didnt-matter/">removed</a> or a region dies off due to lack of oxygen.</p>
<p>For example, sometimes a person with epilepsy doesn’t respond to drugs. Thanks to extraordinary brain imaging techniques, we can potentially work out the exact place in the brain the seizure is starting and remove part of the brain. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="CT brain scans" src="https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/474998/original/file-20220720-20-nqmrpi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">CT scans can reveal ‘missing’ sections of brain due to injury or shrinkage.</span>
<span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/closeup-ct-scan-brain-600w-298101074.jpg">Shutterstock</a></span>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/brain-stimulation-can-rewire-and-heal-damaged-neural-connections-but-it-isnt-clear-how-research-suggests-personalization-may-be-key-to-more-effective-therapies-182491">Brain stimulation can rewire and heal damaged neural connections, but it isn't clear how – research suggests personalization may be key to more effective therapies</a>
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<hr>
<h2>So how does the brain adapt after injury?</h2>
<p>Your brain has about 100 billion neurons and over a trillion synapses (a junction between two neurons, across which an electrical impulse is transmitted). They are constantly rewiring themselves in response to new experiences, to store and retrieve information.</p>
<p>With brain injury, the changes can be bigger; you get certain rewiring around the injury. These synapses can rearrange themselves to work around the damaged part.</p>
<p>Axons (long, threadlike parts of a nerve cell that can conduct electrical impulses) form nerve fibres that get sent out to new spots in response to signals they are getting from the damaged area. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram of components of brain tissue." src="https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=227&fit=crop&dpr=1 600w, https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=227&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=227&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=285&fit=crop&dpr=1 754w, https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=285&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/475004/original/file-20220720-26-asrswp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=285&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Your brain has about 100 billion neurons.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>But there’s another form of plasticity called <a href="https://qbi.uq.edu.au/brain-basics/brain-physiology/what-neurogenesis#:%7E:text=Neurogenesis%20is%20the%20process%20by,birth%20and%20throughout%20our%20lifespan.">neurogenesis</a>. This involves little pockets in the brain where new neurons continue to be born throughout life. And there’s <a href="https://florey.edu.au/science-research/research-teams/stem-cells-and-neural-development-laboratory">evidence</a> that after brain injury these neural stem cells can be stimulated and migrate to the area of injury and make new neurons. </p>
<p>Neurorehabilitation might include physical rehabilitation and speech rehabilitation. And there is also <a href="https://florey.edu.au/science-research/research-teams/epigenetics-and-neural-plasticity-laboratory">research</a> into using drugs to enhance neuroplasticity. That might also apply to slower forms of degeneration such as in Parkinson’s or Huntington’s disease.</p>
<p>As Clarke notes, not everyone has a significant recovery after traumatic brain injury; a lot of people experience ongoing disability. </p>
<p>Many factors affect the way the brain responds to rehabilitation, including the extent and position of the brain injury, genetics, lifestyle and life history.</p>
<p>Some people also experience personality change after a traumatic brain injury.</p>
<p>The textbook case was <a href="https://www.verywellmind.com/phineas-gage-2795244">Phineas Gage</a>, who was involved in an accident in the 1840s that saw a metal rod thrust through his head, destroying a large part of his frontal lobe. He was able to survive and recover but his personality changed. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/post-covid-psychosis-occurs-in-people-with-no-prior-history-the-risk-is-low-but-episodes-are-frightening-179193">Post-COVID psychosis occurs in people with no prior history. The risk is low but episodes are frightening</a>
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<hr>
<h2>What can you do to give your brain its best chance in life?</h2>
<p>I want to end with a message about the five factors of brain health: </p>
<ol>
<li><p>diet: emerging <a href="https://florey.edu.au/events/diet-evolution-gut-health-and-brain-function">evidence</a> shows a relationship between brain health and body health, including your gut microbiome, so ensuring your diet is broadly healthy is good for your brain, as well as the rest of your body</p></li>
<li><p>stress: high levels of chronic stress can be <a href="https://florey.edu.au/science-research/research-projects/defining-the-effects-of-stress-versus-hyperarousal-on-tauopathy-in-alzheime">bad for the brain</a></p></li>
<li><p>sleep: we know good <a href="https://florey.edu.au/science-research/research-teams/sleep-and-cognition">sleep hygiene</a> is very important for a healthy brain</p></li>
<li><p>cognitive or mental <a href="https://florey.edu.au/events/nature-nurture-and-neuroscience-brain-plasticity-in-health-and-disease">exercise</a>: this is uniquely beneficial for the brain and can potentially slow brain ageing</p></li>
<li><p>physical exercise: <a href="https://florey.edu.au/about/news-media/latest-florey-public-lecture-nature-nurture-and-neuroplasticity-now-availab">physical activity</a> is as good for your brain as it is for your body.</p></li>
</ol>
<p>Even though you can’t do anything about your genetics, you can change your lifestyle to give your brain its best chance and potentially slow down brain ageing.</p>
<p>The healthier your brain is, the more likely it will be able to rewire itself and heal if injured, and be resilient to the negative aspects of brain ageing, such as Alzheimer’s disease and other forms of dementia, so these can be delayed or prevented.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-it-about-the-human-brain-that-makes-us-smarter-than-other-animals-new-research-gives-intriguing-answer-183848">What is it about the human brain that makes us smarter than other animals? New research gives intriguing answer</a>
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<img src="https://counter.theconversation.com/content/187285/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anthony Hannan receives funding from the NHMRC and the ARC and some philanthropic funding for medical research.
</span></em></p>The key to understanding how brains can recover from trauma is that they are fantastically plastic – meaning our body’s supercomputer can reshape and remodel itself.Anthony Hannan, Professor and Head of Epigenetics and Neural Plasticity, Florey Institute of Neuroscience and Mental HealthLicensed as Creative Commons – attribution, no derivatives.