tag:theconversation.com,2011:/us/topics/brain-cells-9369/articlesBrain cells – The Conversation2023-03-29T12:28:19Ztag: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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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/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>
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<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">
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<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>
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<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/1925492022-11-02T16:05:33Z2022-11-02T16:05:33ZLab-grown brain cells can play Pong – so should they have legal rights?<figure><img src="https://images.theconversation.com/files/492823/original/file-20221101-12-t5hdnh.jpg?ixlib=rb-1.1.0&rect=131%2C83%2C3820%2C2197&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-illustration/neurons-brain-on-dark-background-3d-700768720">Andrii Vodolazhskyi/Shutterstock</a></span></figcaption></figure><p>The story could have been straight out of science fiction – scientists have grown human brain cells in a lab, and taught them to play the video game <a href="https://www.britannica.com/topic/Pong">Pong</a>, similar to squash or tennis. But this didn’t happen on the big screen. It happened <a href="https://www.bbc.co.uk/news/science-environment-63195653">in a lab in Melbourne</a>, Australia, and it raises the fundamental question of the legal status of these so-called neural networks. </p>
<p>Are they the property of the team that created them, or do they deserve some kind of special status – or even rights? </p>
<p>The reason this question needs to be asked is because the ability to play pong may be a sign that these lab-grown brain cells have achieved <a href="https://plato.stanford.edu/entries/consciousness/">sentience</a> – often defined as the capacity to sense and respond to a world that is external to yourself. And there is widespread consensus that sentience is an important threshold for <a href="https://plato.stanford.edu/entries/grounds-moral-status/">moral status</a>. Ethicists believe that sentient beings are capable of having the moral right not to be treated badly, and an awareness of the implications of sentience is <a href="http://eprints.lse.ac.uk/115111/">increasingly embedded</a> in research practices involving animals.</p>
<p>If the Melbourne neurons are sentient, this may mean they are capable of suffering - perhaps through feeling pain or other avoidable discomfort. As there is broad moral consensus that we should not cause unnecessary suffering, this may mean that there are moral limits on what we can do with these neural networks. </p>
<p>It’s worth saying that the team that created the cells <a href="https://www.cell.com/neuron/fulltext/S0896-6273(22)00806-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627322008066%3Fshowall%3Dtrue">don’t think they are there yet</a> as the closed system in which the experiment took place means that, even if we accept the neurons are responding to an external stimulus, we don’t know whether they are doing so knowingly and with understanding of how their actions can cause certain outcomes. </p>
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<img alt="Image of the game Pong." src="https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/492824/original/file-20221101-26750-2r06ux.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">
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<span class="caption">Pong.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/vhs-tape-screen-capture-simplified-reproduction-1281379615">Grenar/Shutterstock</a></span>
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<p>But given where we are, it’s not beyond the realms of possibility that sentience could be the next milestone. And if this is true, it’s not just ethicists who should be paying attention - legislators should also keep a close eye on this technology. </p>
<h2>The legal problem</h2>
<p>This is because, since Roman times, the law has classified everything as either a person or a property. Legal persons are capable of bearing rights. By contrast, property is something that is incapable of bearing rights. So if we think our neural networks might soon have moral status, and that this ought to be reflected in legal protections, we would need to recognise they were no longer property – but legal persons. And the case of Happy, an elephant at Bronx Zoo who campaigners wanted to transfer to an elephant sanctuary, shows us why this is something we should be proactive about. </p>
<p>The New York courts were recently asked whether Happy had a right to freedom, and they said no – because she was not a legal person. A full overview of the case is <a href="https://theconversation.com/from-ais-to-an-unhappy-elephant-the-legal-question-of-who-is-a-person-is-approaching-a-reckoning-185268">here</a>, but for our purposes, the key thing to take from the judgement is this: the courts accepted Happy was a moral being who was deserving of rights protection, but were powerless to act. That was because changing her legal status from property to person was too big a change for them to make. Instead, it was a job for the legislature – who are choosing to do nothing.</p>
<p>By recognising a moral claim they cannot enforce, the courts – and the law more generally – is perpetuating what it accepts is an injustice. This is especially shocking when you consider that the term “legal person” has never meant the same as “human being”. Throughout history and in legal systems around the world we have seen <a href="https://swarb.co.uk/bumper-development-corporation-ltd-v-commissioner-of-police-of-the-metropolis-ca-1991/">temples</a>, <a href="https://indiankanoon.org/doc/290902/">idols</a>, <a href="https://supreme.justia.com/cases/federal/us/183/424/">ships</a>, <a href="https://tile.loc.gov/storage-services/service/ll/usrep/usrep017/usrep017518/usrep017518.pdf">corporations</a> and even <a href="https://www.parliament.nz/en/get-involved/features/innovative-bill-protects-whanganui-river-with-legal-personhood/">rivers</a> classified as legal persons. Instead, it is just a signifier that the bearer is capable of having legal rights.</p>
<p>The lesson we can take from this is that we need to future-proof the law. It’s better to be proactive to avoid a foreseeable problem than try and play catch-up when it’s already happened.</p>
<p>And as we’ve said above – this problem is foreseeable with regards to the Melbourne neurons. Even if they’re not sentient yet, the potential is there – and so it is something we should take seriously. Because if we accept that these networks are sentient, and do have moral status because of this, then it is desirable that the law reflect this and grant protections commensurate to their interests.</p>
<p>This is not a revolutionary claim, and we have been in a similar place before. When IVF technology first arose in the 1980s, the law had to confront the question of the legal status of in-vitro embryos for the first time. The approach taken was to convene an inquiry to examine the moral questions raised by this new technology, which culminated in recommendations contained in the <a href="https://www.hfea.gov.uk/media/2608/warnock-report-of-the-committee-of-inquiry-into-human-fertilisation-and-embryology-1984.pdf">Warnock report</a>. These recommendations formed the basis of the UK’s legislative framework around IVF, which creates a kind of “third status” for these embryos - not full legal persons, but with significant restrictions on what can be done to them because of their moral status.</p>
<p>The influences of the Warnock report are still visible today - so there is no reason why a similar approach could not be taken with regards to the issues raised in Melbourne. Yes, there are lots of unanswered questions about the capacities of these neural networks and we may very well conclude that they are not deserving of legal protection just yet. </p>
<p>But there are certainly enough questions around this technology to warrant an attempt at finding an answer.</p><img src="https://counter.theconversation.com/content/192549/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joshua Jowitt recently attended a research retreat at the University of Tuebingen on the moral and legal status of human cerebral organoids, which raised similar issues to those contained in this piece. This attendance was fully funded by the German government.</span></em></p>A lump of cells could be given the legal status of a person, or remain a property.Joshua Jowitt, Lecturer in Law, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1701822021-11-18T13:10:39Z2021-11-18T13:10:39ZMapping how the 100 billion cells in the brain all fit together is the brave new world of neuroscience<figure><img src="https://images.theconversation.com/files/432071/original/file-20211115-21-zqihjb.jpg?ixlib=rb-1.1.0&rect=0%2C77%2C2070%2C1264&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Research groups supported by the U.S. BRAIN Initiative recently released the most comprehensive map of cell types in the motor cortex of humans, monkeys and mice.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/paper-brain-royalty-free-image/1252707284">Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p>The brain plays an essential role in how people navigate the world by generating both thought and behavior. Despite being one of the most vital organs of life, it takes up only <a href="https://www.scientificamerican.com/article/does-brain-size-matter1/">2% of human body volume</a>. How can something so small perform such complex tasks?</p>
<p>Luckily, modern tools like brain mapping have allowed <a href="https://scholar.google.com/citations?user=WOQx1ksAAAAJ&hl=en">neuroscientists like me</a> to answer this exact question. By mapping out how all the cell types in the brain are organized and examining how they communicate with one another, neuroscientists can better understand how brains normally work, and what happens when certain cell parts go missing or malfunction.</p>
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<h2>The history of brain mapping</h2>
<p>The task of understanding the inner workings of the brain has fascinated both philosophers and scientists for centuries. <a href="https://web.stanford.edu/class/history13/earlysciencelab/body/brainpages/brain.html">Aristotle</a> proposed that the brain is where spirit resides. <a href="https://dana.org/article/the-hidden-neuroscience-of-leonardo-da-vinci/">Leonardo da Vinci</a> drew anatomical depictions of the brain with wax embedding. And <a href="https://www.nobelprize.org/prizes/medicine/1906/cajal/biographical/">Santiago Ramón y Cajal</a>, with his 1906 Nobel Prize-winning work on the cellular structure of the nervous system, made one of the first breakthroughs that led to modern neuroscience as we know it. </p>
<p>Using a new way to visualize individual cells called <a href="https://embryo.asu.edu/pages/golgi-staining-technique">Golgi staining</a>, a method pioneered by Nobel co-winner Camillo Golgi, and microscopic examination of brain tissue, Cajal established the seminal <a href="https://doi.org/10.1016/j.cub.2006.02.053">neuron doctrine</a>. This principle states that neurons, among the main types of brain cells, communicate with one another via the gaps between them called synapses. These findings launched a race to understand the cellular composition of the brain and how brain cells are connected to one another.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/c-NMfp13Uug?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The CLARITY technique renders whole brains transparent so they can be examined at the molecular level.</span></figcaption>
</figure>
<p>Neuroscience has since experienced a rapid explosion of new experimental tools. Jumping forward 100 years to today, modern tools called <a href="https://doi.org/10.1038/nn0713-771">neurotechniques</a>, which include brain mapping, have given neuroscientists a way to closely inspect every component of the brain. <a href="https://kimlab.io/">My lab</a> has been utilizing these brain mapping tools to understand what cell types make up the brain and how they contribute to the creation of cognition.</p>
<h2>The science of brain mapping</h2>
<p>So how does brain mapping work? </p>
<p>Scientists first need to label, or visualize, a specific cell type. The process is like finding a needle in a haystack – it would be a lot easier to find if the needle, or cell type, glowed. This can be done with either genetic or immunostaining methods. The <a href="https://doi.org/10.1016/j.cell.2018.06.035">genetic method</a> takes advantage of animals, like mice, that can be genetically engineered so only the target cell type is visible under specific fluorescent lights. Immunostaining methods, on the other hand, render brain samples <a href="https://doi.org/10.1038/s41583-019-0250-1">transparent</a> with a special chemical treatment and use antibodies to label the target cell type with a fluorescent tag.</p>
<p>The next step is to image the whole brain using microscopy techniques that allow scientists to view parts too small for the naked eye to see. <a href="https://doi.org/10.1016/j.pbiomolbio.2021.06.013">Specialized microscopy tools</a> can take snapshots, or tiles, of the entire brain. Stitching these image tiles together can reconstruct an intact 3D volume like a photo mosaic. It’s like building a Google map of the brain: By combining millions of individual street photos, you can zoom in to see each street corner and zoom out to see an entire city.</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="Stiched 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">Microscopy tools can stitch together individual image tiles into a photo mosaic of the whole brain. Zooming in on this high-resolution image of a mouse brain reveals rectangular lines where images were stitched together, with each colored dot representing a specific brain 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>Unsurprisingly, this type of 3D imaging creates very large datasets. Even though a mouse brain is <a href="https://dx.doi.org/10.1016%2Fj.neuroimage.2007.05.046">smaller than a human fingertip</a>, the size of these datasets can easily reach between a few hundred gigabytes to a terabyte. Luckily, remarkable advances in computer equipment and software have made large-scale data analysis possible. Artificial intelligence algorithms in particular have enabled scientists to detect many different cell features in the brain, such as cell shape and size, as well as the processes they undergo.</p>
<p>Once scientists are able to detect their target cell type in an image dataset, the final step is to locate specific cell features in a reference brain. This reference brain serves as a standardized map that shows where each brain region is located. Scientists can then use this map to compare with individual brains and note their variations.</p>
<p>These steps are repeated for each cell type, creating a richer and more complete map of the brain with each run-through.</p>
<h2>Working together to build a brain map</h2>
<p>Scientists now have the tools to examine the entire brain in very fine detail. There has been considerable effort to coordinate and pool data from brain mapping research labs to create comprehensive brain maps. For example, the <a href="https://braininitiative.nih.gov/">U.S. BRAIN Initiative</a> created the <a href="https://biccn.org/">BRAIN Initiative Cell Census Network (BICCN)</a> in which my lab participates. Collaborating research groups in the network recently released the most <a href="https://www.nature.com/immersive/d42859-021-00067-2/index.html">comprehensive map of cell types in the brain’s motor cortex</a> across humans, monkeys and mice.</p>
<p>But is this enough to understand how the brain works? </p>
<p>Technical advances in cell staining and microscopy helped Santiago Ramón y Cajal make his pivotal discovery about neurons. However, it was his ability to come up with a theory to explain his observations that advanced neuroscientists’ understanding of the brain.</p>
<p>While researchers have been busy collecting incredibly detailed information about the brain, using this data to create new theories about how the brain works lags behind. A map of cells does not necessarily tell researchers how the cells function and interact with one another as a whole. For example, how do these incredibly complex networks of brain cell types work together to generate cognition? Is there a basic unit in the brain that directs how it forms and functions? Answering questions like these will help researchers understand how specific brain changes are linked to different brain disorders like dementia and come up with new strategies to treat them.</p>
<p>It is a very exciting time for neuroscience research. Incredibly rich, high-resolution brain mapping presents a great opportunity for neuroscientists to deeply ponder what this new data says about how the brain works. Though there are still many unknowns about the brain, these new tools and techniques could help bring them to light.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/170182/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yongsoo Kim receives funding from National Institute of Health.</span></em></p>Scientists have been mapping the brain for centuries. New visualization tools bring them one step closer to understanding where thoughts come from and new ways to treat neurological disorders.Yongsoo Kim, Associate Professor of Neural and Behavioral Sciences, Penn StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1586012021-04-12T12:28:55Z2021-04-12T12:28:55ZAstrocyte cells in the fruit fly brain are an on-off switch that controls when neurons can change and grow<figure><img src="https://images.theconversation.com/files/394301/original/file-20210409-17-yp356o.jpg?ixlib=rb-1.1.0&rect=14%2C44%2C1060%2C668&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The colors in this microscope photo of a fruit fly brain show different types of neurons and the cells that surround them in the brain.</span> <span class="attribution"><a class="source" href="https://www.doelab.org/">Sarah DeGenova Ackerman</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Neuroplasticity – the ability of neurons to <a href="https://doi.org/10.1098/rstb.2016.0158">change their structure and function in response to experiences</a> – can be turned off and on by the cells that surround neurons in the brain, <a href="https://doi.org/10.1038/s41586-021-03441-2">according to a new study</a> on fruit flies that I co-authored.</p>
<p>As fruit fly larvae age, their neurons shift from a highly adaptable state to a stable state and lose their ability to change. During this process, support cells in the brain – called astrocytes – <a href="https://doi.org/10.1016/j.neuron.2017.09.056">envelop the parts of the neurons</a> that send and receive electrical information. When my team removed the astrocytes, the neurons in the fruit fly larvae remained plastic longer, hinting that somehow astrocytes suppress a neuron’s ability to change. We then discovered two specific proteins that regulate neuroplasticity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Fruit flies on a table." src="https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=388&fit=crop&dpr=1 600w, https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=388&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=388&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=488&fit=crop&dpr=1 754w, https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=488&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/394336/original/file-20210409-17-346mnx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=488&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">As fruit flies develop, special cells surround their neurons and seem to halt neuroplasticity.</span>
<span class="attribution"><span class="source">Sarah DeGenova Ackerman</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>The human brain is made up of billions of neurons that form complex connections with one another. Flexibility at these connections is a <a href="https://doi.org/10.1073/pnas.1820836117">major driver of learning and memory</a>, but things can go wrong if it isn’t tightly regulated. For example, in people, too much plasticity at the wrong time is linked to brain disorders such as <a href="https://doi.org/10.1016/j.cub.2015.09.040">epilepsy</a> and <a href="https://doi.org/10.1016/S0896-6273(00)81109-5">Alzheimer’s disease</a>. Additionally, reduced levels of the two neuroplasticity-controlling proteins we identified are linked to increased susceptibility to <a href="https://doi.org/10.3389/fncel.2018.00470">autism</a> and <a href="https://doi.org/10.1038/s41380-020-00944-8">schizophrenia</a>.</p>
<p>Similarly, in our fruit flies, removing the cellular brakes on plasticity permanently impaired their crawling behavior. While fruit flies are of course different from humans, their brains work in very similar ways to the human brain and can offer valuable insight.</p>
<p>One obvious benefit of discovering the effect of these proteins is the potential to treat some neurological diseases. But since a neuron’s flexibility is closely tied to learning and memory, in theory, researchers might be able to <a href="https://doi.org/10.1111/nyas.12682">boost plasticity</a> in a controlled way to <a href="https://doi.org/10.1098/rstb.2013.0288">enhance cognition in adults</a>. This could, for example, allow people to more easily learn a new language or musical instrument. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A colorful microscope image of a developing fruit fly brain." src="https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=342&fit=crop&dpr=1 600w, https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=342&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=342&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=430&fit=crop&dpr=1 754w, https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=430&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/394317/original/file-20210409-13-1a039sz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=430&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In this image showing a developing fruit fly brain on the right and the attached nerve cord on the left, the astrocytes are labeled in different colors showing their wide distribution among neurons.</span>
<span class="attribution"><span class="source">Sarah DeGenova Ackerman</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>How we did the work</h2>
<p><a href="https://scholar.google.com/citations?user=-sssMIEAAAAJ&hl=en&oi=sra">My colleagues and I</a> focused our experiments on a specific type of neurons called motor neurons. These control movements like <a href="https://doi.org/10.1186/s13064-018-0103-z">crawling</a> and <a href="https://doi.org/10.1002/cne.903400311">flying</a> in fruit flies. To figure out how astrocytes controlled neuroplasticity, we used genetic tools to turn off specific proteins in the astrocytes one by one and then measured the effect on motor neuron structure. We found that astrocytes and motor neurons communicate with one another using a specific pair of proteins called neuroligins and neurexins. These proteins essentially function as an off button for <a href="https://doi.org/10.1038/s41586-021-03441-2">motor neuron plasticity</a>.</p>
<h2>What still isn’t known</h2>
<p>My team discovered that two proteins can control neuroplasticity, but we don’t know how these cues from astrocytes cause neurons to lose their ability to change.</p>
<p>Additionally, researchers still know very little about why neuroplasticity is so strong in younger animals and <a href="https://doi.org/10.1073/pnas.1820836117">relatively weak in adulthood</a>. In our study, we showed that prolonging plasticity beyond development can sometimes be <a href="https://doi.org/10.1038/s41586-021-03441-2">harmful to behavior</a>, but we don’t yet know why that is, either. </p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p>
<h2>What’s next</h2>
<p>I want to explore why longer periods of neuroplasticity can be harmful. Fruit flies are great study organisms for this research because it is very easy to <a href="https://doi.org/10.1038/nmeth.1567">modify the neural connections in their brains</a>. In my team’s next project, we hope to determine how changes in neuroplasticity during development can lead to long–term changes in behavior.</p>
<p>There is so much more work to be done, but our research is a first step toward treatments that use astrocytes to influence how neurons change in the mature brain. If researchers can understand the basic mechanisms that control neuroplasticity, they will be one step closer to developing therapies to treat a variety of neurological disorders.</p>
<p><em>To learn more about Sarah DeGenova Ackerman’s research on fruit flies and neuroplasticity, tune in to this episode of The Conversation Weekly podcast.</em></p>
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<p class="fine-print"><em><span>Sarah DeGenova Ackerman receives funding from the NIH/NINDS. Sarah DeGenova Ackerman is a Milton Safenowitz postdoctoral fellow of the ALS Association.</span></em></p>Adaptable neurons are tied to learning and memory but also to neurological disorders. By studying fruit flies, researchers found a mechanism that controls neuroplasticity.Sarah DeGenova Ackerman, Postdoctoral Fellow, UO Institute of Neuroscience and Howard Hughes Medical Institute, University of OregonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1505012020-12-03T13:01:29Z2020-12-03T13:01:29ZThis brain protein may be key to treating Parkinson’s – study in rats shows<figure><img src="https://images.theconversation.com/files/372801/original/file-20201203-13-12dbfo8.jpg?ixlib=rb-1.1.0&rect=8%2C0%2C5742%2C3837&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The protein, called GDF5, plays an important role in the development and function of certain brain neurons.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-woman-holding-seniors-hands-leaning-1382470571">pikselstock/ Shutterstock</a></span></figcaption></figure><p>Parkinson’s disease, a brain disorder that affects over <a href="https://doi.org/10.1007/s00702-017-1686-y">10 million people worldwide</a>, is caused by the gradual loss of <a href="https://doi.org/10.3410/B2-2">dopamine neurons</a>. The loss of these neurons leads to involuntary tremors, stiffness and balance problems. While there are drugs to treat these symptoms, no drugs exist to slow the progression of the disease. However, we found a brain protein that may be able to prevent the loss of dopamine neurons. This discovery could be important for developing treatments.</p>
<p>For many years, scientists have been investigating the <a href="https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(20)30217-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614720302170%3Fshowall%3Dtrue">use of neurotrophic factors</a> to slow the progression of Parkinson’s disease. These proteins are normally found in the brain and play an important role in protecting and nurturing different types of neurons, including dopamine neurons, which are critical for controlling movement.</p>
<p>In 1993, one neurotrophic factor, called glial cell line-derived neurotrophic factor (GDNF), was found to <a href="https://science.sciencemag.org/content/260/5111/1130.long">protect dopamine neurons</a> in laboratory tests. Following extensive laboratory studies in which GDNF displayed much benefit, clinical trials were started in the early 2000s. </p>
<p>In these trials, GDNF was administered directly into the brains of Parkinson’s patients. <a href="https://doi.org/10.1038/nm850">Promising results</a> were reported from the <a href="https://doi.org/10.3171/jns.2005.102.2.0216">early trials</a>, in which small numbers of patients all received GDNF treatment. Researchers became excited about the potential of using neurotrophic factors to treat Parkinson’s disease. </p>
<p>But to prove that a treatment is effective, it must be tested in clinical trials in which patients are randomly allocated to receive the experimental drug or a placebo. A GDNF clinical trial was established, but unfortunately, it showed that treating the brain with GDNF <a href="https://doi.org/10.1002/ana.20737">did not significantly improve</a> movement symptoms in patients with Parkinson’s when compared with patients who received the placebo. </p>
<p>Despite attempts to improve the delivery of GDNF to the brain, a 2019 placebo-controlled clinical trial of GDNF still produced <a href="https://doi.org/10.1093/brain/awz023">disappointing results</a>. This was a huge blow to the Parkinson’s community and has led to researchers questioning the potential benefit of neurotrophic factors. </p>
<figure class="align-center ">
<img alt="An illustration of a brain-derive neurotrophic factor molecule." src="https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=482&fit=crop&dpr=1 600w, https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=482&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=482&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=606&fit=crop&dpr=1 754w, https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=606&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/372803/original/file-20201203-23-d3yas9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=606&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A brain-derived neurotrophic factor (BDNF) molecule.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/brainderived-neurotrophic-factor-bdnf-protein-molecule-369119558">StudioMolekuul/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But our research has found promise in another neurotrophic factor, called GDF5. This neurotrophic factor is related to GDNF, but it exerts its effects on dopamine neurons by working in a different way. GDF5 plays an important role in the normal development and functioning of dopamine neurons. Our laboratory studies have shown that GDF5 has protective effects on these neurons, which are as potent as the effects of GDNF.</p>
<p>Our <a href="https://doi.org/10.1093/brain/awaa367">most recent study</a>, published in the journal Brain, found that GDF5 had beneficial effects in a rat model of Parkinson’s, in which GDNF was previously shown to be ineffective. This particular rat model allowed us to more closely mimic human Parkinson’s disease than those rat models that had been used in the earlier studies on GDNF – and which had lead to the clinical trials being approved. </p>
<p>For our study, we administered an excess of alpha-synuclein (a protein that is thought to be involved in Parkinson’s) in the brain to replicate Parkinson’s disease. We then delivered the gene to produce human GDF5 protein to the brain. Six months later, we counted the numbers of dopamine neurons in the brain. We found that about 40-50% of dopamine neurons had died in the untreated group, but this was not seen in the group treated with GDF5. We also found that GDF5 increased the amount of dopamine in the brain. Our next step is to study what stage of the disease it’s best to deliver GDF5 to the brain to slow the disease’s progression.</p>
<p>One reason that researchers have put forward to explain the failure of the GDNF clinical trials is that a <a href="https://stm.sciencemag.org/content/4/163/163ra156.editor-summary">protein called RET</a> may be destroyed in the brain when a person develops Parkinson’s. RET is needed for GDNF to act on dopamine neurons. But GDF5 acts through a different pathway – so does not need RET. Our study also found that the cell components needed for GDF5 to act on dopamine neurons are not destroyed by Parkinson’s disease. </p>
<p>The most important findings that we have made are that GDF5 has protective effects on dopamine neurons in the best known laboratory model of Parkinson’s and that the cell components needed for GDF5 to work are not destroyed by Parkinson’s disease. These are very promising results and mean that the search for a new therapy for Parkinson’s focusing on neurotrophic factors should continue.</p><img src="https://counter.theconversation.com/content/150501/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerard O'Keeffe receives funding from Science Foundation Ireland.</span></em></p><p class="fine-print"><em><span>Aideen Sullivan 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>Neurotrophic factors play an important role in protecting neurons – which is why researchers are investigating them as a treatment for Parkinson’s.Gerard O'Keeffe, Professor in Anatomy and Neuroscience, University College CorkAideen Sullivan, Professor in Neuroscience, University College CorkLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1422402020-09-24T12:26:02Z2020-09-24T12:26:02ZThe neural cruelty of captivity: Keeping large mammals in zoos and aquariums damages their brains<figure><img src="https://images.theconversation.com/files/349253/original/file-20200723-33-1boc6lr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3346%2C2232&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Photograph of an elephant brain. </span> <span class="attribution"><a class="source" href="https://www.wits.ac.za/staff/academic-a-z-listing/m/man/paulmangerwitsacza/">Dr. Paul Manger/ University of the Witwatersrand, Johannesburg</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p><a href="http://elephantsinjapan.com/worlds-loneliest-elephant-hanako/">Hanako</a>, a female Asian elephant, lived in a tiny concrete enclosure at Japan’s Inokashira Park Zoo for more than 60 years, often in chains, with no stimulation. In the wild, <a href="https://www.elephantvoices.org/elephant-sense-a-sociality-4/elephants-are-socially-complex.html">elephants live in herds</a>, with close family ties. Hanako was solitary for the last decade of her life. </p>
<p><a href="https://whalesanctuaryproject.org/whales/kiska-alone-again/">Kiska</a>, a young female orca, was captured in 1978 off the Iceland coast and taken to Marineland Canada, an aquarium and amusement park. Orcas are social animals that live in family <a href="https://www.nationalgeographic.com/animals/mammals/o/orca/">pods</a> with up to 40 members, but Kiska has lived alone in a small tank since 2011. Each of her five calves died. To combat stress and boredom, she swims in slow, endless circles and has gnawed her teeth to the pulp on her concrete pool.</p>
<p>Unfortunately, these are common conditions for many large, captive mammals in the “entertainment” industry. In decades of <a href="https://scholar.google.com/citations?user=KvCW9T0AAAAJ&hl=en">studying the brains of humans, African elephants, humpback whales and other large mammals</a>, I’ve noted the organ’s great sensitivity to the environment, including serious impacts on its structure and function from living in captivity. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=560&fit=crop&dpr=1 600w, https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=560&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=560&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=704&fit=crop&dpr=1 754w, https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=704&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/349255/original/file-20200723-31-16bcfav.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=704&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Hanako, an Asian elephant kept at Japan’s Inokashira Park Zoo; and Kiska, an orca that lives at Marineland Canada. One image depicts Kiska’s damaged teeth.</span>
<span class="attribution"><span class="source">Elephants in Japan (left image), Ontario Captive Animal Watch (right image)</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Affecting health and altering behavior</h2>
<p>It is easy to observe the overall health and psychological consequences of life in captivity for these animals. Many captive elephants suffer from arthritis, obesity or skin problems. Both <a href="https://doi.org/10.11609/JoTT.o2620.1826-36">elephants</a> and orcas often have severe dental problems. Captive orcas are plagued by <a href="https://doi.org/10.1016/j.jveb.2019.05.005">pneumonia, kidney disease, gastrointestinal illnesses and infections</a>. </p>
<p>Many animals <a href="https://doi.org/10.1016/j.neubiorev.2017.09.010">try to cope</a> with captivity by adopting abnormal behaviors. Some develop “<a href="https://doi.org/10.1016/j.applanim.2017.05.003">stereotypies</a>,” which are repetitive, purposeless habits such as constantly bobbing their heads, swaying incessantly or chewing on the bars of their cages. Others, especially big cats, pace their enclosures. Elephants rub or break their tusks. </p>
<h2>Changing brain structure</h2>
<p>Neuroscientific research indicates that living in an impoverished, stressful captive environment <a href="https://doi.org/10.1016/j.jveb.2019.05.005">physically damages the brain</a>. These changes have been documented in many <a href="https://doi.org/10.1002/cne.903270108">species</a>, including rodents, rabbits, cats and <a href="https://doi.org/10.1006/nimg.2001.0917">humans</a>. </p>
<p>Although researchers have directly studied some animal brains, most of what we know comes from observing animal behavior, analyzing stress hormone levels in the blood and applying knowledge gained from a half-century of neuroscience research. Laboratory research also suggests that mammals in a zoo or aquarium have compromised brain function. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=803&fit=crop&dpr=1 600w, https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=803&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=803&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1008&fit=crop&dpr=1 754w, https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1008&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/359445/original/file-20200922-16-gunhd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1008&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 illustration shows differences in the brain’s cerebral cortex in animals held in impoverished (captive) and enriched (natural) environments. Impoverishment results in thinning of the cortex, a decreased blood supply, less support for neurons and decreased connectivity among neurons.</span>
<span class="attribution"><span class="source">Arnold B. Scheibel</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Subsisting in confined, barren quarters that lack intellectual stimulation or appropriate social contact seems to <a href="https://doi.org/10.1590/S0001-37652001000200006">thin the cerebral cortex</a> – the part of the brain involved in voluntary movement and higher cognitive function, including memory, planning and decision-making.</p>
<p>There are other consequences. Capillaries shrink, depriving the brain of the oxygen-rich blood it needs to survive. Neurons become smaller, and their dendrites – the branches that form connections with other neurons – become less complex, impairing communication within the brain. As a result, the cortical neurons in captive animals <a href="https://doi.org/10.1002/cne.901230110">process information less efficiently</a> than those living in <a href="https://doi.org/10.1002/dev.420020208">enriched, more natural environments</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=500&fit=crop&dpr=1 754w, https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=500&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/349257/original/file-20200723-25-16c33n4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=500&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 actual cortical neuron in a wild African elephant living in its natural habitat compared with a hypothesized cortical neuron from a captive elephant.</span>
<span class="attribution"><span class="source">Bob Jacobs</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Brain health is also affected by living in small quarters that <a href="https://doi.org/10.3233/BPL-160040">don’t allow for needed exercise</a>. Physical activity increases the flow of blood to the brain, which requires large amounts of oxygen. Exercise increases the production of new connections and <a href="http://dx.doi.org/10.1126/science.aaw2622">enhances cognitive abilities</a>.</p>
<p>In their native habits these animals must move to survive, covering great distances to forage or find a mate. Elephants
typically travel anywhere from <a href="https://www.elephantsforafrica.org/elephant-facts/#:%7E:text=How%20far%20do%20elephants%20walk,km%20on%20a%20daily%20basis.">15 to 120 miles per day</a>. In a zoo, they average <a href="https://doi.org/10.1371/journal.pone.0150331">three miles daily</a>, often walking back and forth in small enclosures. One free orca studied in Canada swam <a href="https://doi.org/10.1007/s00300-010-0958-x">up to 156 miles a day</a>; meanwhile, an average orca tank is about 10,000 times smaller than its <a href="https://www.cascadiaresearch.org/projects/killer-whales/using-dtags-study-acoustics-and-behavior-southern">natural home range</a>. </p>
<h2>Disrupting brain chemistry and killing cells</h2>
<p>Living in enclosures that restrict or prevent normal behavior creates chronic frustration and boredom. In the wild, an animal’s stress-response system helps it escape from danger. But captivity traps animals with <a href="https://doi.org/10.1073/pnas.1215502109">almost no control</a> over their environment. </p>
<p>These situations foster <a href="https://doi.org/10.1037/rev0000033">learned helplessness</a>, negatively impacting the <a href="https://doi.org/10.1155/2016/6391686">hippocampus</a>, which handles memory functions, and the <a href="https://doi.org/10.1016/j.neuropharm.2011.02.024">amygdala</a>, which processes emotions. Prolonged stress <a href="https://doi.org/10.3109/10253899609001092">elevates stress hormones</a> and <a href="https://doi.org/10.1523/JNEUROSCI.10-09-02897.1990">damages or even kills neurons</a> in both brain regions. It also disrupts the <a href="https://doi.org/10.1016/j.neubiorev.2005.03.021">delicate balance of serotonin</a>, a neurotransmitter that stabilizes mood, among other functions.</p>
<p>In humans, <a href="https://doi.org/10.1006/nimg.2001.0917">deprivation</a> can trigger <a href="https://doi.org/10.3389/fnins.2018.00367">psychiatric issues</a>, including depression, anxiety, <a href="https://doi.org/10.3389/fnins.2018.00367">mood disorders</a> or <a href="https://doi.org/10.1177/1073858409333072">post-traumatic stress disorder</a>. <a href="https://doi.org/10.1007/s00429-010-0288-3">Elephants</a>, <a href="https://doi.org/10.1371/journal.pbio.0050139">orcas</a> and other animals with large brains are likely to react in similar ways to life in a severely stressful environment. </p>
<h2>Damaged wiring</h2>
<p>Captivity can damage the brain’s complex circuitry, including the basal ganglia. This group of neurons communicates with the cerebral cortex along two networks: a direct pathway that enhances movement and behavior, and an indirect pathway that inhibits them. </p>
<p>The repetitive, <a href="http://dx.doi.org/10.1016/j.bbr.2014.05.057">stereotypic behaviors</a> that many animals adopt in captivity are caused by an imbalance of two neurotransmitters, dopamine and <a href="https://doi.org/10.1016/j.neubiorev.2010.02.004">serotonin</a>. This impairs the indirect pathway’s ability to modulate movement, a condition documented in species from chickens, cows, sheep and horses to primates and big cats.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Image of brain showing areas affected by captivity" src="https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/349258/original/file-20200723-17-dzrjt3.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">The cerebral cortex, hippocampus and amygdala are physically altered by captivity, along with brain circuitry that involves the basal ganglia.</span>
<span class="attribution"><span class="source">Bob Jacobs</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Evolution has constructed animal brains to be exquisitely responsive to their environment. Those reactions can affect neural function by <a href="https://www.penguinrandomhouse.com/books/311787/behave-by-robert-m-sapolsky/">turning different genes on or off</a>. Living in inappropriate or abusive circumstance alters biochemical processes: It disrupts the synthesis of proteins that build connections between brain cells and the neurotransmitters that facilitate communication among them. </p>
<p>There is strong evidence that <a href="https://doi.org/10.1523/JNEUROSCI.0577-11.2011">enrichment</a>, social contact and appropriate space in more natural habitats are <a href="https://doi.org/10.1111/j.1748-1090.2003.tb02071.x">necessary</a> for long-lived animals with large brains such as <a href="https://doi.org/10.1371/journal.pone.0152490">elephants</a> and <a href="https://doi.org/10.1080/13880292.2017.1309858">cetaceans</a>. Better conditions <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543669/">reduce disturbing sterotypical behaviors</a>, improve connections in the brain, and <a href="https://doi.org/10.1038/cdd.2009.193">trigger neurochemical changes</a> that enhance learning and memory. </p>
<h2>The captivity question</h2>
<p>Some people defend keeping animals in captivity, arguing that it helps conserve endangered species or offers educational benefits for <a href="http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.574.3479&rep=rep1&type=pdf">visitors to zoos and aquariums</a>. These justifications are questionable, particularly for <a href="https://animalstudiesrepository.org/acwp_zoae/8/">large mammals</a>. As my own research and work by many other scientists shows, caging large mammals and putting them on display is undeniably cruel from a neural perspective. It causes brain damage. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>Public perceptions of captivity are slowly changing, as shown by the reaction to the documentary <a href="https://en.wikipedia.org/wiki/Blackfish_(film)">“Blackfish</a>.” For animals that cannot be free, there are well-designed sanctuaries. Several already exist for elephants and other large mammals in <a href="https://www.elephants.com/">Tennessee</a>, <a href="https://globalelephants.org/overview/">Brazil</a> and Northern <a href="http://www.pawsweb.org/about_our_sanctuaries.html">California</a>. Others are being developed for large <a href="https://whalesanctuaryproject.org/">cetaceans</a>. </p>
<p>Perhaps it is not too late for Kiska. </p>
<p><em>Dr. Lori Marino, president of the <a href="https://whalesanctuaryproject.org/">Whale Sanctuary Project</a> and a former senior lecturer at Emory University, contributed to this article.</em></p><img src="https://counter.theconversation.com/content/142240/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bob Jacobs 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>Life in captivity causes observable harm to the structure and function of large mammals’ brains.Bob Jacobs, Professor of Neuroscience, Colorado CollegeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1414372020-07-08T12:13:26Z2020-07-08T12:13:26ZSynthetic odors created by activating brain cells help neuroscientists understand how smell works<figure><img src="https://images.theconversation.com/files/346129/original/file-20200707-194405-awzgsl.jpg?ixlib=rb-1.1.0&rect=767%2C8%2C4838%2C3242&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When you sniff a particular scent, your brain cells fire in a recognizable pattern.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/young-woman-smelling-perfume-from-bottle-at-royalty-free-image/953961844">Maskot via Getty Images</a></span></figcaption></figure><p>When you experience something with your senses, it evokes complex patterns of activity in your brain. One important goal in neuroscience is to decipher how these neural patterns drive the sensory experience.</p>
<p>For example, can the smell of chocolate be represented by a single brain cell, groups of cells firing all at the same time or cells firing in some precise symphony? The answers to these questions will lead to a broader understanding of how our brains represent the external world. They also have implications for treating disorders where the brain fails in representing the external world: for example, in the loss of sight of smell.</p>
<p>To understand how the brain drives sensory experience, <a href="https://rinberglab.com">my colleagues and I</a> focus on the sense of smell in mice. We directly control a mouse’s neural activity, <a href="https://doi.org/10.1126/science.aba2357">generating “synthetic smells”</a> in the olfactory part of its brain in order to learn more about how the sense of smell works.</p>
<p>Our latest experiments discovered that scents are represented by very specific patterns of activity in the brain. Like the notes of a melody, the cells fire in a unique sequence with particular timing to represent the sensation of smelling a unique odor.</p>
<h2>Scents produced by light projections</h2>
<p>Using mice to study smell is appealing to researchers because the <a href="https://doi.org/10.1016/j.conb.2018.04.008">relevant brain circuits have been mapped out</a>, and modern tools allow us to directly manipulate these brain connections.</p>
<p>The mice we use are genetically engineered so we can activate individual brain cells simply by shining light of specific wavelengths onto them – <a href="https://doi.org/10.1038/nn1525">a technique known as optogenetics</a>. Early uses of optogenetics involved light delivered through implanted optical fibers, letting researchers control coarse patches of brain cells. More recent uses of optogenetics allow <a href="https://doi.org/10.1126/science.aaw5202">more sophisticated control</a> of <a href="https://doi.org/10.1016/j.cell.2019.05.045">precise patterns of brain activity</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=393&fit=crop&dpr=1 600w, https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=393&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=393&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=494&fit=crop&dpr=1 754w, https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=494&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/346080/original/file-20200707-22-1rfavl2.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=494&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 simplified image of a mouse brain, looking down from the top. The olfactory bulb (left) is at the front of the brain and receives connections from receptor cells in the nose.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Mouse_brain_top_view.png">Database Center for Life Science/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>For our study, we projected light patterns onto the surface of the brain, targeting a region known as the olfactory bulb. Previous research has found that when mice sniff different scents, cells in the olfactory bulb appear to fire in a sort of patterned symphony, with a <a href="https://doi.org/10.1152/jn.90902.2008">unique pattern formed in response to each distinct smell</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=617&fit=crop&dpr=1 600w, https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=617&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=617&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=776&fit=crop&dpr=1 754w, https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=776&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/346101/original/file-20200707-194405-1ojhb4o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=776&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Rather than receiving sensory signals from the nose, the olfactory bulb was activated by light projections.</span>
<span class="attribution"><span class="source">Edmund Chong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>When we shined light patterns onto a mouse’s olfactory bulb, it generated corresponding patterns of cellular activity. We called these patterns “synthetic smells.” As opposed to a pattern of activity triggered by a mouse sniffing a real odor, we directly triggered the neural activity of a “synthetic smell” with our light projections.</p>
<p>Next we trained each individual mouse to recognize a randomly generated synthetic smell. Since they can’t describe to us in words what they’re perceiving, we rewarded each mouse with water if it licked a water spout whenever it detected its assigned smell. Over weeks of training, mice learned to lick when their assigned smell was activated, and not to lick for other randomly generated synthetic smells. </p>
<p>[<em><a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=experts">Expertise in your inbox. Sign up for The Conversation’s newsletter and get expert takes on today’s news, every day.</a></em>]</p>
<p>We cannot say for sure that these synthetic smells correspond to any known odor in the world, nor do we know what they smell like to the mouse. But we did calibrate our synthetic patterns to broadly resemble olfactory bulb patterns observed when actual scents are present. Furthermore, mice learn to discriminate synthetic smells about as quickly as they did real smells.</p>
<h2>Tweaking the pattern of a synthetic smell</h2>
<p>Once each mouse learned to recognize its assigned synthetic smell, we measured how much they still licked when we modified the assigned smell. Within each synthetic pattern, we altered which cells were activated or when they activated.</p>
<p>Imagine taking a familiar song, changing individual notes in the song, and asking whether you still recognized the song after each change. By testing many different changes, one can eventually understand which precise composition of notes is essential to the song’s identity and which tweaks are extreme enough to make the song unrecognizable.</p>
<p>Likewise, by measuring how mice changed their licking as we modified their projected light patterns, we were able to understand which combinations of cells within the pattern were important for identifying the synthetic smell.</p>
<p>The precise combination of cells activated was crucial. But just as important was when they are activated in an ordered sequence, akin to timed notes in a melody. For example, changing the order of cells in the sequence would render the smell unrecognizable.</p>
<p>It turned out that the cells activated earlier in the sequence were more important for recognition – changing the sequences later in the pattern seemed to have negligible effects.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/lJ2bof_fWgM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Watch an animation of how these sequences in the brain work.</span></figcaption>
</figure>
<p>Changes in recognition were graded, and not drastic: When we changed small parts of the pattern, the smell did not become completely unrecognizable. In fact, the degree to which the smell was recognized was proportional to the degree of change in the pattern. This implies that if I slightly modify the brain activity that represents an orange, you would still smell something similar – maybe recognizing it as citrus, or fruity.</p>
<p>So while the brain has huge capacity to store many different smells in unique timed sequences of cell activity, you can still recognize similar smells by the similarity in their patterns: The smell of coffee is still distinctly recognizable even with a splash of vanilla added to it. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/346134/original/file-20200707-194418-1oc455r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&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 know the smell of coffee even if it’s served with a dash of fragrant vanilla.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/hot-espresso-royalty-free-image/981402468">Roland Beerli/500px Prime via Getty Images</a></span>
</figcaption>
</figure>
<p>The next step in this research is to bring the synthetic approach to real smells. To do so, we would need to record brain activity in response to a real smell, then reactivate the very same cells using optogenetics. The synthetic re-creation of real objects in the brain is the current focus of research in <a href="https://doi.org/10.1126/science.aaw5202">multiple</a> <a href="https://doi.org/10.1016/j.cell.2019.05.045">labs</a> <a href="https://doi.org/10.1364/BRAIN.2019.BM3A.2">including ours</a>.</p>
<p>Addressing this issue is exciting because it opens up possibilities not just for understanding how the brain works, but also for developing brain implants that may one day restore the loss of sensory experiences.</p><img src="https://counter.theconversation.com/content/141437/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Edmund Chong 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>Brains recognize a smell based on which cells fire, in what order – the same way you recognize a song based on its pattern of notes. How much can you change the ‘tune’ and still know the smell?Edmund Chong, Ph.D. Student in Neuroscience, New York UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1392322020-05-27T10:31:29Z2020-05-27T10:31:29ZMicroglia: the brain’s ‘immune cells’ protect against diseases – but they can also cause them<figure><img src="https://images.theconversation.com/files/337896/original/file-20200527-20229-2g5qgy.jpg?ixlib=rb-1.1.0&rect=8%2C0%2C2986%2C2100&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The microglia (in red) can both protect against and contribute to diseases like Alzheimer's.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/microglia-cells-red-play-important-role-1421646863">Juan Gaertner/ Shutterstock</a></span></figcaption></figure><p>We know that the body’s immune system is important for keeping everything in check and protecting us. But a lot of us don’t realise that the brain also has an immune system.</p>
<p>Microglia, which are the brain’s immune system cells, are involved in everything – from brain development to protecting against diseases such as <a href="https://pubmed.ncbi.nlm.nih.gov/25744564/">meningitis</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997862/">Alzheimer’s</a>. But for all the good these cells do for us, under the wrong conditions they can also cause us harm.</p>
<p>Microglia belong to a group of non-neuronal cells called glia, which originally were thought to play a supportive role for the brain’s neurons. Now research shows that microglia actually do much more than only support the neurons: they nourish, protect and sometimes even destroy them. </p>
<p>These cells are unique because they come from the same place as other immune system cells, but have a different origin from other brain cells, which develop from neural stem cells. Microglia come from the <a href="https://pubmed.ncbi.nlm.nih.gov/23616747/">yolk sac</a> – an extra embryonic membrane – and travel to the brain <a href="https://www.frontiersin.org/articles/10.3389/fncel.2013.00045/full">early during its development</a>.</p>
<p>Once established, microglia perform numerous functions. They <a href="https://www.cell.com/trends/cell-biology/pdf/S0962-8924(16)00029-5.pdf">help neurons connect</a>, clean the brain of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640215/">waste and dead or injured cells</a>, constantly check <a href="https://www.sciencedirect.com/science/article/pii/S2211124719306217">everything is in order</a>, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC523558/">defend the brain</a> from external threats (such as microbes), and internal threats <a href="https://pubmed.ncbi.nlm.nih.gov/29769333/">including misfolded proteins</a> (when a protein takes on the wrong form, which can cause disease). Their ability to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079257">change physical form and behaviour</a> in response to their environment allows them to perform these many roles. </p>
<p>Microglial functions are especially crucial during brain development, when they <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099170/">help young neurons grow</a>, and ensure the right connections are made between neurons. Through a procedure called <a href="https://www.sciencedirect.com/science/article/abs/pii/S0959438815001828">pruning</a>, microglia eat connections between neurons, maintaining strong ones while eliminating weaker or unnecessary ones. This continues somewhat during adulthood. For example, microglia remove unimportant memories by <a href="https://www.sciencenews.org/article/brain-microglia-memories-forgetting">eating or altering synapses</a> involved in their maintenance.</p>
<p>Faulty pruning during brain development has been linked with disorders such as <a href="https://www.nature.com/articles/s41593-018-0334-7">schizophrenia</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/25845529/">autism</a>. But uncontrollable pruning by microglia in adulthood has been implicated in developing diseases such as <a href="https://www.jneurosci.org/content/38/12/2911">Alzheimer’s</a>.</p>
<p>Microglia have specific receptors on their surface which recognise distress signals from other cells. These signals <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242927/">attract microglia</a> to the site of the problem. When the brain’s balance is disturbed (usually as a result of inflammation), living neurons can become stressed and <a href="https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14323">produce these signals</a>. This may cause them to be eaten alive by microglia. As neurons are killed, the connections they have with other neurons are also eliminated, which can cause severe issues in brain connectivity and functions. </p>
<p>Inflammation in the brain can be caused by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476783/">stress</a>, <a href="https://jamanetwork.com/journals/jamaneurology/fullarticle/793256">pathogens, and auto-immune conditions</a>, and is also connected to inflammation in <a href="https://pubmed.ncbi.nlm.nih.gov/30830722/">other parts of the body</a>. Brain inflammation is common in neurodegenerative diseases, as well as mental health disorders, including <a href="https://www.hgi.org.uk/resources/delve-our-extensive-library/depression/brain-inflamed">depression</a>.</p>
<p>Inflammation causes microglia to change roles, and turn into their aggressive form to defend the brain. Usually, when stress signals stop and anti-inflammatory signals are received, microglia go back to first repairing, then <a href="https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-11-98">protecting the brain</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=360&fit=crop&dpr=1 600w, https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=360&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=360&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=453&fit=crop&dpr=1 754w, https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=453&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/337901/original/file-20200527-20219-1nb4xg7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=453&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Even ageing can make our microglia more aggressive.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/old-hands-solving-jigsaw-puzzle-nursing-166336454">Robert Kneschke/ Shutterstock</a></span>
</figcaption>
</figure>
<p>But there are cases, such as with <a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159111005654">chronic stress</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553257/">ageing</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/24638131/">neurodegenerative disorders</a>, where microglia can become more aggressive and less easy to regulate, making them more dangerous for the brain. In these cases, microglia can increase in numbers, unnecessarily kill nearby cells, and may contribute to making the brain even more inflamed by secreting inflammatory molecules. They also <a href="https://link.springer.com/article/10.1007/s12035-019-1529-y">don’t go back</a> to their protective role easily. </p>
<h2>Look after your brain</h2>
<p>But there are many things we can do to keep our microglia happy – and our brains healthy – such as:</p>
<p><strong>Maintain a healthy diet:</strong> Compounds found in fruits, vegetables, and healthy fats, can keep your <a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159114004784">microglia young</a>, and shift them <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058829/">towards an anti-inflammatory form</a>.</p>
<p><strong>Keep your gut bacteria happy:</strong> The brain and the gut are connected by the <a href="https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00044/full">vagus nerve</a>, so microbes living in our gut have a large effect on the brain. These microorganisms are involved in the <a href="https://www.alzforum.org/news/research-news/be-hale-and-hearty-brain-microglia-need-healthy-gut">development, maintenance, and overall health</a> of microglia.</p>
<p><strong>Avoid alcohol and smoking:</strong> Alcohol causes brain damage. <a href="https://www.jimmunol.org/node/85560.full">A recent study</a> found that one of the ways it does so is by activating the microglia’s inflammatory response. Research shows this activation is also induced by a <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2009.06203.x">specific compound found in cigarette smoke</a>.</p>
<p><strong>Sleep:</strong> <a href="https://www.sciencedaily.com/releases/2019/10/191021111835.htm">Microglia never sleep</a>, but they clean and repair the brain and improve memory while you do. <a href="https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0998-z">Lack of sleep</a>, however, has also been shown to make microglia take on their inflammatory form.</p>
<p><strong>Take care of your mental health:</strong> <a href="https://www.sciencedirect.com/science/article/abs/pii/S1084952118300855">Microglia can sense stress</a>, and they respond to it by turning into their inflammatory form. This form is present in numerous <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758507/">neuropsychiatric disorders</a>, and also in some cases mental health issues (such as depression) that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674029/">precede neurodegenerative disorders</a>. </p>
<p>It has also been shown that anti-inflammatory treatment can help with <a href="https://www.sciencedaily.com/releases/2019/10/191028213923.htm">managing the symptoms of psychiatric disorders</a>, and that some medications used for the treatment of mental health issues have <a href="https://pubmed.ncbi.nlm.nih.gov/28342944/">an anti-inflammatory element</a>. Antidepressants have also been shown to directly <a href="https://link.springer.com/chapter/10.1007/978-81-322-2803-5_36">regulate microglia responses</a>. </p>
<p><strong>Exercise:</strong> A recent review found exercise directly affects microglia, and shifts them towards having a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678635/">protective form</a>. Exercising the brain has also been shown to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596759/">train microglia to resist Alzheimer’s disease</a>.</p>
<p>Although we know some things about microglia, we don’t know everything. We know some things about how they form, that they’re involved in many diseases, and that they might essentially control the brain. But we also know we can’t control them. Future research might focus on how we can stop microglia from causing diseases, and how to stop these cells from turning against the brain.</p><img src="https://counter.theconversation.com/content/139232/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eleftheria Kodosaki 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>Between 10-15% of all cells within the brain are microglia.Eleftheria Kodosaki, Academic associate, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1312412020-02-06T19:34:45Z2020-02-06T19:34:45ZBrain cells long thought of as passive play key role in memory – study in mice<figure><img src="https://images.theconversation.com/files/313950/original/file-20200206-43084-sbvivc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rat microglia in green.</span> <span class="attribution"><span class="source">wikipedia</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Microglia are resident immune cells in your brain that act as first responders, always on the lookout for trouble. Accounting for about <a href="https://www.ncbi.nlm.nih.gov/pubmed/10567732">10% of our brain cells</a>, they were historically thought of as passive bystanders in the brain until injury or infection kicked them into action. These cells were first observed in 1856 by the German <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2603088/">physician Rudolf Virchow</a> and later termed microglia, which means “small glue”.</p>
<p>Now a new study in mice, <a href="https://science.sciencemag.org/cgi/doi/10.1126/science.aaz2288">published in Science</a>, shows that microglia may actually be key players in memory retention. If the same effect is discovered in humans, it may lead to better treatment of amnesia, Alzheimer’s and other conditions affecting memory.</p>
<p>Microglia have many jobs. When there is an injury or infection present, they play an active role in dampening the brain’s response. But scientists are increasingly realising that microglia have many jobs. Our brains are messy places with cells dying and chemicals building up that need to be cleared. It’s the job of microglia to keep our brains highways clear and healthy.</p>
<p>Scientists have also recently shown that microglia are involved in maintaining connections between the nerve cells known as synpases. These are vital communication junctions in order to allow brain cells to talk to each other and transmit brain signals. Specifically, during brain development, microglia actively <a href="https://www.ncbi.nlm.nih.gov/pubmed/21778362/">remove or “prune” synapses</a> and this helps to shape the circuitry that makes your brain work efficiently. </p>
<p>In fact, it is these connections between nerve cells that hold our memories and are susceptible to attack in diseases that affect our memory, such as Alzheimer’s disease. For that reason, there is a growing interest across the scientific community in these cells and the potential to provide new targets for treating complex brain disease, such as Alzheimer’s disease.</p>
<p>Indeed, a gene known to elevate an individual’s risk factor for developing Alzheimer’s disease is TREM-2, which <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595327/">encodes a protein found in microglia.</a> </p>
<h2>Memory retention</h2>
<p>The new study indicates that microglia are closely involved in memory retention in mice. Mice underwent a fear conditioning task which led them to freeze with fear when placed in an environment in which they remembered experiencing something negative – in this study a small electric shock to their feet. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=482&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=482&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=482&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=606&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=606&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313719/original/file-20200205-149789-5ixbj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=606&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Image showing microglia in the mouse brain. Microglia were stained red.</span>
<span class="attribution"><span class="source">Chao Wang</span></span>
</figcaption>
</figure>
<p>Over a period of 35 days, the freezing responses of the mice diminished from 70% to 20% – indicating that they had forgotten the negative association with that specific environment. The authors then used an array of scientific tools including genetic, pharmacological and biochemical approaches to get rid of microglia within the brains of these mice and did the experiment all over again.</p>
<p>The results revealed that removing microglia altered their response to this task. Some 50% of the mice (compared to the 20% above) still remembered the negative experience even after a similar period.
The assumption here is that microglia hold the key to cementing these memories and underpinning what is forgotten and what is retained. The study goes on to show that it is the rearranging of the connections within the mice that leads to this observation.</p>
<p>While this is an exciting study for the science community, what does it mean for advancing the understanding of the human brain and our own ability to forget? It is important to remember that the picture in the human brain is more than likely to be something quite different. There is now growing evidence of the distinct differences between mouse and human microglia. </p>
<p>These studies have looked at what makes up both human and mice microglia and <a href="https://www.nature.com/articles/s41586-019-0924-x">found some differences</a> in how they respond to injury. That means that their response to brain maintenance may also be shaped very differently. </p>
<p>So while it looks like the job description for microglia just got a little more complex, the mystery surrounding human microglia and their role in forgetfulness still needs to be explored. But it is possible, as suggested in genetic studies, that these cells do also play some sort of important role in human memory function.</p><img src="https://counter.theconversation.com/content/131241/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Dallas 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>A new study raises hopes of better treatment for amnesia, Alzheimer’s and other conditions affecting memory.Mark Dallas, Associate Professor in Cellular Neuroscience, University of ReadingLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1273982019-11-26T16:07:48Z2019-11-26T16:07:48ZYour big brain makes you human – count your neurons when you count your blessings<figure><img src="https://images.theconversation.com/files/303790/original/file-20191126-112531-8ucpjc.jpg?ixlib=rb-1.1.0&rect=18%2C350%2C3101%2C1904&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's these brain cells that really make humans unique.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/various-types-brain-cells-seamless-doodle-387830680">anyaivanova/Shutterstock.com</a></span></figcaption></figure><p>Here’s something new to consider being thankful for at Thanksgiving: the long evolutionary journey that gave you your big brain and your long life. </p>
<p>Courtesy of our <a href="https://mitpress.mit.edu/books/human-advantage-1">primate ancestors that invented cooking over a million years ago</a>, you are a member of the one species able to afford <a href="https://www.ted.com/talks/suzana_herculano_houzel_what_is_so_special_about_the_human_brain?language=en">so many cortical neurons in its brain</a>. With them come the <a href="https://www.newswise.com/articles/lifespan-and-sexual-maturity-depends-on-your-brain-more-than-your-body">extended childhood and the pushing century-long lifespan</a> that together make human beings unique.</p>
<p>All these bequests of your bigger brain cortex mean you can gather four generations around a meal to exchange banter and gossip, <a href="https://www.youtube.com/watch?v=EvSA1qhBq4M">turn information into knowledge</a> and even practice the art of what-not-to-say-when.</p>
<p>You may even want to be thankful for another achievement of our neuron-crammed human cortices: <a href="https://mitpress.mit.edu/books/human-advantage-1">all the technology</a> that allows people spread over the globe to come together in person, on screens, or through words whispered directly into your ears long distance.</p>
<p>I know I am thankful. But then, <a href="https://scholar.google.com/citations?user=cldyZo8AAAAJ&hl=en&oi=ao">I’m the one</a> proposing that we humans <a href="https://doi.org/10.1016/bs.pbr.2019.06.001">revise the way we tell the story</a> of how our species came to be. </p>
<h2>Brains made of cells, but how many?</h2>
<p>Back when I had just received my freshly minted Ph.D. in neuroscience and started working in science communication, I found out that 6 in 10 college-educated people believed they <a href="https://doi.org/10.1177/107385840200800206">only used 10% of their brains</a>. I’m glad to say that they’re wrong: We use all of it, just in different ways at different times.</p>
<p>The myth seemed to be supported by statements in serious textbooks and scientific articles that “the <a href="https://www.verywellmind.com/how-many-neurons-are-in-the-brain-2794889">human brain is made of 100 billion neurons</a> and 10 times as many supporting glial cells.” I wondered if those numbers were facts or guesses. Did anyone actually know that those were the <a href="https://news.vanderbilt.edu/vanderbiltmagazine/brainiac-with-her-innovative-brain-soup-suzana-herculano-houzel-is-changing-neuroscience-one-species-at-a-time/">numbers of cells in the human brain</a>?</p>
<p>No, <a href="https://doi.org/10.1002/cne.24040">they didn’t</a>.</p>
<p>Neuroscientists did have a rough idea. Some estimates suggested 10 to 20 billion neurons for the human cerebral cortex, others some 60 to 80 billion in another region called the cerebellum. With the rest of the brain known to be fairly sparse in comparison, the number of neurons in the whole human brain was definitely closer to 100 billion than to just 10 billion (far too little) or 1 trillion (way too many).</p>
<p>But there we were, neuroscientists armed with fancy tools to modify genes and light up parts of the brain, still in the dark about what different brains were made of and how the human brain compared to others.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=238&fit=crop&dpr=1 600w, https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=238&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=238&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=299&fit=crop&dpr=1 754w, https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=299&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/303755/original/file-20191126-112526-hy3her.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=299&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Slicing up different animals’ brains – like this one from an elephant – is the first step.</span>
<span class="attribution"><span class="source">Suzana Herculano-Houzel</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Counting up neurons in brain soup</h2>
<p>So I devised a way to <a href="https://doi.org/10.1523/JNEUROSCI.4526-04.2005">easily and rapidly count</a> how many cells a brain is made of. I <a href="https://www.karger.com/Article/FullText/437413">spent 15 years collecting brains</a> and then turning them into soup that I examined under the microscope. That’s how I got the hard numbers.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=219&fit=crop&dpr=1 600w, https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=219&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=219&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=275&fit=crop&dpr=1 754w, https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=275&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/303759/original/file-20191126-112512-1yynyg6.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=275&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 elephant brain is bigger than a human one, but its number of cortical neurons is smaller.</span>
<span class="attribution"><a class="source" href="http://doi.org/10.3389/neuro.09.031.2009">Drawings by Lorena Kaz</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>As it turned out, there are many ways to put brains together: <a href="https://doi.org/10.1073/pnas.1201895109">Primates like us have more neurons in the cerebral cortex</a> than most other mammals, no matter the size of the brain. A brain can be large but made of relatively few neurons if those neurons are huge, like in an elephant; primate neurons are small, and bird neurons are even tinier, so even the <a href="https://doi.org/10.1073/pnas.1517131113">smallest bird brains can hide lots of neurons</a>. But never as many as the largest primate brain: ours. </p>
<p>When comparing brains, we care about numbers of neurons in the cortex because it’s the area of the brain that lets us go beyond the simple detection and response to stimuli, allowing us to learn from the past and make plans for the future.</p>
<p>Because neurons are the Lego pieces that build brains and process information, the <a href="https://doi.org/10.1016/j.cobeha.2017.02.004">more cortical neurons a species has</a>, the more flexible and complex that species’ cognition can be, regardless of size. And not just that: I recently found that the more cortical neurons, the <a href="https://doi.org/10.1002/cne.24564">longer the species takes to develop into adulthood</a>, just like it takes longer to assemble a truckload of Legos into a mansion than a handful into a little house. And for as yet unknown reasons, <a href="https://doi.org/10.1002/cne.24564">along with more cortical neurons comes a longer life</a>.</p>
<p>Getting more cortical neurons thus seems to be a two-for-one bargain: Buy <a href="https://doi.org/10.1016/bs.pbr.2019.06.001">more mental capabilities, and along comes more lifetime</a> to learn to use them.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=433&fit=crop&dpr=1 600w, https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=433&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=433&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=544&fit=crop&dpr=1 754w, https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=544&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/303766/original/file-20191126-112517-1fwokgy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=544&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">No more rough estimates. The average male human brain contains 86 billion neurons and 85 billion non-neuronal cells.</span>
<span class="attribution"><span class="source">Suzana Herculano-Houzel</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Powering all those neurons</h2>
<p><a href="https://doi.org/10.1371/journal.pone.0017514">Lots more neurons cost lots more energy</a>, though. </p>
<p>If people had kept exclusively eating raw foods, like all other primates do, they would need to spend <a href="https://doi.org/10.1073/pnas.1206390109">over nine hours every single day</a> searching, collecting, picking and eating to feed their <a href="https://doi.org/10.3389/neuro.09.031.2009">16 billion cortical neurons</a>. Forget about discovering electricity or building airplanes. <a href="https://doi.org/10.1098/rspb.2015.1853">There would be no time</a> for looking at the stars and wondering about what could be. Our great ape cousins, ever the raw foodies, still have at most <a href="https://doi.org/10.1159/000322729">half as many cortical neurons as we do</a> – and they eat over eight hours per day.</p>
<p>But our ancestors figured out how to cheat nature to get more from less, first with stone tools and later with fire. They invented cooking and <a href="https://www.basicbooks.com/titles/richard-wrangham/catching-fire/9780786744787/">changed human history</a>. Eating is faster and much more efficient, not to say <a href="https://doi.org/10.1016/j.jhevol.2008.03.003">delicious</a>, when food is pre-processed and transformed with fire.</p>
<p>With plenty of calories available in much less time, new generations gained bigger and bigger brains. And the more cortical neurons they had, the longer kids remained kids, the longer their parents lived, and the more the former could learn from the latter, then from grandparents, and even great-grandparents. Cultures soon flourished. Technology bloomed and lived on through schooling and science, becoming ever more complex.</p>
<p>With so much culture to share, what makes us modern humans has become about <a href="https://doi.org/10.1016/bs.pbr.2019.06.001">much more than our human biology</a>. Being born with lots of neurons gives us the potential for a long and slow life, one where each of our brains gets a chance to be educated by what the generations before us have learned, and to educate the next ones. We will remain modern humans so long as we are willing to convene around dinner tables to celebrate our differences and to share our hard-earned knowledge, stories of success and failure, our hopes and dreams. </p>
<p>
<section class="inline-content">
<img src="https://images.theconversation.com/files/248895/original/file-20181204-133100-t34yqm.png?w=128&h=128">
<div>
<header>Suzana Herculano-Houzel is the author of:</header>
<p><a href="https://mitpress.mit.edu/books/human-advantage-1">The Human Advantage: How Our Brains Became Remarkable</a></p>
<footer>MIT Press provides funding as a member of The Conversation US.</footer>
</div>
</section>
</p><img src="https://counter.theconversation.com/content/127398/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>We have more neurons in our cortices than any other species, courtesy of an early technology – and along with them came our long, slow lives, with plenty of chances to gather around the dinner table.Suzana Herculano-Houzel, Associate Professor of Psychology, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1029522018-09-11T13:15:14Z2018-09-11T13:15:14ZCurious Kids: if the universe is like a giant brain, then where’s its body?<figure><img src="https://images.theconversation.com/files/235751/original/file-20180911-144482-1wpcxvv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Observable_universe#/media/File:Large-scale_structure_of_light_distribution_in_the_universe.jpg">Andrew Pontzen, Fabio Governato/Wikimedia Commons.</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p><em>This is an article from <a href="https://theconversation.com/au/topics/curious-kids-36782">Curious Kids</a>, a series for children of all ages. The Conversation is asking young people to send in questions they’d like an expert to answer. All questions are welcome: find out how to enter at the bottom.</em> </p>
<hr>
<blockquote>
<p><strong>The universe looks like a giant brain. If it’s the brain, where’s the body? – Aine, age 12, Edinburgh, UK</strong></p>
</blockquote>
<p>Thanks for the question, Aine. Let’s start by looking at the picture of brain cells on the left. Then take a look at the picture of the cosmic web – which maps out the universe – on the right. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"999144265073811456"}"></div></p>
<p>The two do seem very similar, when you look at them side by side. So it’s easy to think that the universe we live in might be the brain of a giant body. But actually, there’s another reason why the cosmic web and the brain cells look so alike: it’s because the laws of physics are the same everywhere. </p>
<p>Over the course of human history, scientists have learnt about the laws of physics by studying how matter and energy act in the universe. From the tiniest atom to the biggest galaxy, everything in the universe obeys these laws of physics. But just because everything follows the same laws, doesn’t mean everything is the same. </p>
<p>The shapes we see when we look at the cosmic web are created by <a href="https://theconversation.com/curious-kids-how-does-gravity-pull-things-down-to-earth-101545">the force of gravity</a>, invisible <a href="https://www.esa.int/esaKIDSen/SEM2RDW2EMH_OurUniverse_0.html">dark matter</a> (which we don’t know very much about at all) and changes caused by violent and powerful events, such as exploding stars called supernovae. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=291&fit=crop&dpr=1 600w, https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=291&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=291&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=366&fit=crop&dpr=1 754w, https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=366&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/235773/original/file-20180911-144464-9p1cnd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=366&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">What’s left over from a supernova.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/hubble_esa/8691557901/sizes/l">Hubble Space Telescope(ESA)/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Our brains are definitely not caused by big cosmic events. Actually, the shape of our brains comes from billions of years of evolution. Evolution happens because each generation of animals (including humans) passes on the features and behaviours which helped it to survive in its environment to its children.</p>
<p>Your brain looks the way it does because storing brain cells this way means information can travel really quickly from one part of the brain to another. We’re like this because our ancestors had to use their brains to respond to their environment very quickly, to survive – imagine having to escape from a tiger that was trying to hunt you! </p>
<p>This trait was passed down from generation to generation, and we still have it today – except now, we’re more likely to use it for passing exams than running away from tigers.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/PD2XgQOyCCk?wmode=transparent&start=225" frameborder="0" allowfullscreen=""></iframe>
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<p>But our brains are still made of the same atoms and molecules as the rest of the universe. And the shape of our brains and the universe are related to a branch of mathematics called <a href="https://theconversation.com/explainer-what-are-fractals-10865">“fractals”</a>. A fractal is a pattern that repeats itself, no matter how close or far away you get.</p>
<p>Much of physics is dependent on processes such as fractals, so there are also many things in nature which act like fractals: from the path of rivers down to the ocean, to the delicate shape of a snowflake. Even cities act as fractals: look at photographs of the world at night, from space, and you’ll see similar patterns. Neither the universe, nor our brains are perfect fractals – but they are close. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/235770/original/file-20180911-144455-15bpe08.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Cities in Europe, lit up at night.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nasamarshall/6093337721/sizes/o/">NASA's Marshall Space Flight Center/Flickr.</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>There’s one final reason why the universe might look so much like a brain, in a picture. The universe is so big, and our brains are so small, that we can’t see either of these things very well – even though we have strong microscopes and telescopes, which have helped us a lot. </p>
<p>Because of this, scientists often use computer models to show us what things look like, and how they behave. A computer model is like a miniature version of what we want to study. So instead of trying to look at teeny tiny brain cells, or huge parts of the universe, we can just look at what happens in the model. </p>
<p>Even though the scientists who study brains are trying to solve very different problems to the scientists who study the universe, the computer programs they use are quite similar. So, when these scientists create images using computer models, the images can look quite similar – even if they’re of completely different things. </p>
<p>For example, both images might have a bright patch where there’s lots of activity (like big groups of galaxies, or brain cells) and a darker patch where there’s none. This can sometimes make us think that two very different things might be more connected than they really are.</p>
<p>Every day, scientists in both fields are finding out new things about the universe and the bodies we exist in. If you want to become a scientist, maybe one day you can help make these discoveries too. </p>
<hr>
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<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/165749/original/image-20170419-32713-1kyojyz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p><em>Please tell us your name, age and which town or city you live in. You can send an audio recording of your question too, if you want. Send as many questions as you like! We won’t be able to answer every question, but we will do our best.</em></p>
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<p><em>More <a href="https://theconversation.com/topics/curious-kids-36782?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=CuriousKidsUK">Curious Kids</a> articles, written by academic experts:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/curious-kids-how-does-our-heart-beat-102609?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=CuriousKidsUK">How does our heart beat? – Aarav, age nine, Mumbai, India</a></em></p></li>
<li><p><em><a href="https://theconversation.com/curious-kids-how-do-birds-see-where-theyre-going-101932?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=CuriousKidsUK">How do birds see where they’re going? – Thomas and Luke, age six, Sussex, UK</a></em></p></li>
<li><p><em><a href="https://theconversation.com/curious-kids-do-butterflies-remember-being-caterpillars-99508?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=CuriousKidsUK">Do butterflies remember being caterpillars? – Evan, age five, Bristol, UK</a></em></p></li>
</ul><img src="https://counter.theconversation.com/content/102952/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maya Horton receives funding from the Science and Technology Facilities Council (STFC).</span></em></p>Our brain cells do look a lot like a map of the universe – but that doesn’t mean they’re the same thing.Maya Horton, PhD Candidate, University of HertfordshireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/931832018-03-14T10:49:47Z2018-03-14T10:49:47ZControversial brain study has scientists rethinking neuron research<figure><img src="https://images.theconversation.com/files/210020/original/file-20180313-30954-l9is0w.jpg?ixlib=rb-1.1.0&rect=289%2C0%2C3156%2C1922&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Could it be that a baby has all the brain cells she ever will?</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/2Lb835v61Qo">Jv Garcia on Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Scientists have known for about two decades that some neurons – the fundamental cells in the brain that transmit signals – are <a href="http://www.jneurosci.org/content/22/3/614">generated throughout life</a>. But now a controversial new study from the University of California, San Francisco, casts doubt on whether many <a href="https://doi.org/10.1038/nature25975">neurons are added to the human brain after birth</a>.</p>
<p><a href="https://scholar.google.com/citations?user=J8IBQ_8AAAAJ&hl=en">As a translational neuroscientist</a>, this work immediately piqued my interest. It has direct implications for the <a href="http://naegelelab.research.wesleyan.edu">research my lab does</a>: We transplant young neurons into damaged brain areas in mice in an attempt to treat epileptic seizures and the damage they’ve caused. Like many labs, part of our work is based on a foundational belief that the hippocampus is a brain region where new neurons are born throughout life.</p>
<p>If the new study is right, and human brains for the most part don’t add new neurons after infancy, researchers like me need to reconsider the validity of the animal models we use to understand various brain conditions – in my case temporal lobe epilepsy. And I suspect other labs that focus on conditions including drug addiction, depression and post-traumatic stress disorder are thinking about what the UCSF study means for their investigations, too. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=473&fit=crop&dpr=1 600w, https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=473&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=473&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=595&fit=crop&dpr=1 754w, https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=595&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/210098/original/file-20180313-30983-17040k8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=595&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In the brain of a baby who died soon after birth, there are many new neurons (green in this image) in the hippocampus.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/nature25975">Sorrells et al</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>When and where are new neurons born?</h2>
<p>No doubt, the adult human brain is able to learn throughout life and to change and adapt – a capability brain scientists call neuroplasticity, the <a href="https://theconversation.com/what-is-brain-plasticity-and-why-is-it-so-important-55967">brain’s ability to reorganize itself by rewiring connections</a>. Yet, a central dogma in the field of neuroscience for nearly 100 years had been that a child is <a href="https://doi.org/10.1093/acprof:oso/9780195065169.001.0001">born with all the neurons she will ever have</a> because the adult brain cannot regenerate neurons. </p>
<p>Just over half a century ago, researchers devised a way to study proliferation of cells in the mature brain, based on <a href="https://doi.org/10.1038/35036235">techniques to incorporate a radioactive label</a> into new cells as they divide. This approach led to the startling discovery in the 1960s that <a href="https://doi.org/10.1002/cne.901370404">rodent brains actually could generate new neurons</a>. </p>
<p>Neurogenesis – the production of new neurons – was previously thought to only occur during embryonic life, a time of extremely rapid brain growth and expansion, and the rodent findings were met with considerable skepticism. Then researchers discovered that new neurons are also <a href="http://www.pnas.org/content/80/8/2390.short">born throughout life in the songbird brain</a>, a species scientists use as a model for studying vocal learning. It started to look like neurogenesis plays a key role in learning and neuroplasticity – at least in some brain regions in a few animal species. </p>
<p>Even so, neuroscientists were skeptical that many nerve cells could be renewed in the adult brain; evidence was scant that dividing cells in mammalian brains produced new neurons, as opposed to other cell types. It wasn’t until researchers extracted neural stem cells from adult mouse brains and grew them in cell culture that scientists showed these precursor cells could <a href="https://doi.org/10.1073/pnas.90.5.2074">divide and differentiate into new neurons</a>. Now it is generally well accepted that neurogenesis takes place in two areas of the adult rodent brain: the olfactory bulbs, which process smell information, and the hippocampus, a region characterized by neuroplasticity that is required for forming new declarative memories.</p>
<p>Adult neural stem cells cluster together in what scientists call niches – <a href="https://doi.org/10.1016/j.devcel.2015.01.010">hotbeds for cultivating the birth and growth of new neurons</a>, recognizable by their distinctive architecture. Despite the mounting evidence for regional growth of new neurons, these studies underscored the point that the adult brain harbors only a few stem cell niches and their capacity to produce neurons is limited to just a few types of cells. </p>
<p>With this knowledge, and new tools for labeling proliferating cells and identifying maturing neurons, scientists began to look for postnatal neurogenesis in primate and human brains.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/210140/original/file-20180313-30989-51senu.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">A mouse neural stem cell (blue and green) grows in a lab dish. Can human brain cells do what rodent brain cells do?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/34021671492">Mark McClendon, Zaida Alvarez Pinto, Samuel I. Stupp, Northwestern University, Evanston, IL</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<h2>What’s happening in adult human brains?</h2>
<p>Many neuroscientists believe that by understanding the process of adult neurogenesis we’ll gain insights into the causes of some human neurological disorders. Then the next logical step would be trying to develop new treatments harnessing neurogenesis for conditions such as Alzheimer’s disease or trauma-induced epilepsy. And stimulating resident stem cells in the brain to generate new neurons is an exciting prospect for treating neurodegenerative diseases.</p>
<p>Because neurogenesis and learning in rodents <a href="https://doi.org/10.1523/JNEUROSCI.1731-05.2005">increases with voluntary exercise</a> and <a href="https://doi.org/10.1159/000368575">decreases with age</a> and <a href="https://doi.org/10.1101/cshperspect.a021303">early life stress</a>, some workers in the field became convinced that older people might be able to enhance their memory as they age by maintaining a program of <a href="https://doi.org/10.1073/pnas.1015950108">regular aerobic exercise</a>.</p>
<p>However, obtaining rigorous proof for adult neurogenesis in the human and primate brain has been technically challenging – both due to the limited experimental approaches and the larger sizes of the brains, compared to reptiles, songbirds and rodents.</p>
<p>Researchers injected a compound found in DNA, nicknamed BrdU to <a href="https://doi.org/10.1038/3305">identify brand new neurons in human adult hippocampus</a> – but the labeled cells were extremely rare. Other groups demonstrated that adult human brain tissue obtained during neurosurgery contained stem cell niches that housed progenitor cells that <a href="https://doi.org/10.1038/nature02301">could generate new neurons in the lab</a>, showing that these cells had an inborn neurogenic capacity, even in adults.</p>
<p>But even when scientists saw evidence for new neurons in the brain, they tended to be scarce. Some neurogenesis experts were skeptical that evidence based on incorporating BrdU into DNA was a reliable method for proving that new cells were actually being born through cell division, rather than just serving as a <a href="http://www.jneurosci.org/content/22/3/614.long">marker for other normal cell functions</a>.</p>
<p>Further questions about how long human brains retain the capacity for neurogenesis arose in 2011, with a study that compared numbers of <a href="https://doi.org/10.1038/nature10487">newborn neurons migrating</a> in the olfactory bulbs of infants versus older individuals up to 84 years of age. Strikingly, in the first six months of life, the baby brains contained lots of chains of young neurons <a href="https://doi.org/10.1126/science.aaf7073">migrating into the frontal lobes</a>, regions that guide executive function, long-range planning and social interactions. These areas of the human cortex are hugely increased in size and complexity compared to rodents and other species. But between 6 to 18 months of age, the migrating chains dwindled to a thin stream. Then, a very different pattern emerged: Where the migrating chains of neurons had been in the infant brain, a cell-free gap appeared, suggesting that neural stem cells become depleted during the first six months of life. </p>
<p>Questions still lingered about the human hippocampus and adult neurogenesis as a source for its neuroplasticity. One group came up with a clever approach based on radiocarbon dating. They measured how much atmospheric ¹⁴C – a radioactive isotope derived from nuclear bomb tests – was incorporated into people’s DNA. This method suggested that as many as <a href="https://doi.org/10.1016/j.cell.2013.05.002">700 new cells are added to the adult human hippocampus every day</a>. But these findings were contradicted by a 2016 study that found that the neurogenic cells in the adult hippocampus <a href="https://doi.org/10.1111/nan.12337">could only produce non-neuronal brain cells called microglia</a>. </p>
<h2>Rethinking neurogenesis research</h2>
<p>Now the largest and most comprehensive study conducted to date <a href="https://theconversation.com/adult-human-brains-dont-grow-new-neurons-in-hippocampus-contrary-to-prevailing-view-93123">presents even stronger evidence</a> that robust neurogenesis doesn’t continue throughout adulthood in the human hippocampus – or if it does persist, it is extremely rare. This work is controversial and not universally accepted. Critics have been <a href="https://www.statnews.com/2018/03/07/adult-brains-neurogenesis/">quick to cast doubt on the results</a>, but the finding isn’t totally out of the blue. </p>
<p>So where does this leave the field of neuroscience? If the UCSF scientists are correct, what does that mean for ongoing research in labs around the world?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=385&fit=crop&dpr=1 600w, https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=385&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=385&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=483&fit=crop&dpr=1 754w, https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=483&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/210092/original/file-20180313-30983-74xzrf.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=483&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’s much easier to work with rodent brains than human ones. This is a stained image of the hippocampus and neurons of a mouse with neurodegenerative disease.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/nichd/22028646372">NICHD/I. Williams</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Because lots of studies of neurological diseases are done in mice and rats, many scientists are invested in the possibility that adult neurogenesis persists in the human brain, just as it does in rodents. If it doesn’t, how valid is it to think that the mechanisms of learning and neuroplasticity in our model animals are comparable to those in the human brain? How relevant are our models of neurological disorders for understanding how changes in the hippocampus contribute to disorders such as the type of epilepsy I study? </p>
<p>In my lab, we transplant embryonic mouse or human neurons <a href="https://doi.org/10.1523/JNEUROSCI.0005-14.2014">into the adult hippocampus in mice, after damage caused by epileptic seizures</a>. We aim to repair this damage and suppress seizures by seeding the mouse hippocampus with neural stem cells that will mature and form new connections. In temporal lobe epilepsy, studies in adult rodents suggest that naturally occurring hippocampal neurogenesis is problematic. It seems that the newborn hippocampal neurons become highly excitable and contribute to seizures. We’re trying to inhibit these newborn hyperexcitable neurons with the transplants. But if humans don’t generate new hippocampal neurons, then maybe we’re developing a treatment in mice for a problem that has a different mechanism in people.</p>
<p>Perhaps our species has evolved separate mechanisms for neuroplasticity, distinct from those used by species such as rats and mice. One possibility is that there are other sites in the human brain where neurogenesis occurs - its a big structure and more exploration will be necessary. If it turns out to be true that the human brain has a diminished capacity for neurogenesis after birth, the finding will have important implications for how neuroscientists like me think about tackling brain disorders.</p>
<p>Perhaps most importantly, this work underscores how crucial it is to learn how to increase the longevity of the neurons we do have, born early in life, and how we might replace or repair neurons that become damaged.</p><img src="https://counter.theconversation.com/content/93183/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Janice R. Naegele receives funding from the National Institutes of Health, Connecticut Regenerative Medicine Fund and CURE Epilepsy.</span></em></p>Neuroscience labs around the world may need to reevaluate some of their assumptions about whether what works in animals will really produce meaningful treatments for people.Janice R. Naegele, Alan M Dachs Professor of Science, Professor of Biology, Neuroscience and Behavior, Wesleyan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/867992017-11-03T16:21:52Z2017-11-03T16:21:52ZHere’s what we think Alzheimer’s does to the brain<figure><img src="https://images.theconversation.com/files/193167/original/file-20171103-26426-1nurx5m.jpg?ixlib=rb-1.1.0&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>Around <a href="https://www.alz.co.uk/research/statistics">50m people</a> worldwide are thought to have Alzheimer’s disease. And with rapidly ageing populations in many countries, the number of sufferers is steadily rising.</p>
<p>We know that Alzheimer’s is caused by problems in the brain. Cells begin to lose their functions and eventually die, <a href="https://www.alzheimersresearchuk.org/about-dementia/types-of-dementia/alzheimers-disease/symptoms/">leading to</a> memory loss, a decline in thinking abilities and even major personality changes. Specific regions of the brain also shrink, a process <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821835/">known as atrophy</a>, causing a significant loss of brain volume. But what’s actually happening in the brain to cause this?</p>
<p>The main way the disease works is to disrupt communication between neurons, the specialised cells that process and transmit electrical and chemical signals between regions of the brain. This is what is responsible for the cell death in the brain – and we think its due to a build up of two types of protein, called <a href="https://www.ncbi.nlm.nih.gov/pubmed/24493463">amyloid and tau</a>. The exact interaction between these two proteins is largely unknown, but amyloid accumulates into sticky clusters known as beta-amyloid “plaques”, while tau builds up inside dying cells as “neurofibrillary tangles”.</p>
<p>One of the difficulties of diagnosing Alzheimer’s is that we’ve no reliable and accurate way of measuring this protein build-up during the early stages of the disease. In fact, we can’t definitively diagnose Alzheimer’s until after the patient has died, by examining their actual brain tissue.</p>
<p>Another problem we have is that beta-amyloid plaques can also be found in the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737680/">brains of healthy patients</a>. This suggests the presence of the amyloid and tau proteins may not tell the whole story of the disease. </p>
<p>More recent research suggests <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506930/">chronic inflammation</a> may play a role. Inflammation is part of the body’s defence system against disease and occurs when white blood cells release chemicals to protect the body from foreign substances. But, over a long enough period, it can also cause damage.</p>
<p>In the brain, tissue-damaging long-term inflammation can also be caused by a build-up of cells known as microglia. In a healthy brain, these cells engulf and destroy waste and toxins. But in Alzheimer’s patients, the microglia fail to clear away this debris, which can include toxic tau tangles or amyloid plaques. The body then activates more microglia to try to clear the waste but this in turn causes inflammation. Long-term or chronic inflammation is particularly damaging to brain cells and ultimately leads to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653290/">brain cell death</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/193170/original/file-20171103-26456-1lb75ql.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">Declining abilities.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Scientists recently identified a gene called TREM2 that could be responsible for this problem. Normally TREM2 acts to guide microglia to clear beta-amyloid plaques from the brain, and to help fight inflammation within the brain. But <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427527/">researchers have found</a> that the brains of patients whose TREM2 gene doesn’t work properly have a build-up of beta-amyloid plaques between neurons. </p>
<p>Many Alzheimer’s patients also experience problems with their heart and circulatory system. Beta-amyloid deposits in the brain arteries, atherosclerosis (hardening of the arteries), and mini-strokes <a href="http://journals.sagepub.com/doi/abs/10.1177/1533317516653820?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&">may also be at play</a>.</p>
<p>These “vascular” problems can reduce blood flow in the brain even more and break down the blood-brain barrier, a structure that is critical for removing toxic waste from the brain. This can also prevent the brain from absorbing as much glucose – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881550">some studies</a> have suggested this may actually occur before the onset of toxic proteins associated within Alzheimer’s disease within the brain. </p>
<h2>Personalised treatment</h2>
<p>More recently, researchers have been looking deeper into the brain, specifically at the precise connections between neurons, known as synapses. <a href="https://www.nature.com/articles/s41467-017-00867-z">A recent study</a> published in Nature describes a process in the cells that may contribute to the breakdown of these synaptic communications between neurons. The findings indicate that this may happen when there isn’t enough of a specific synaptic protein (known as RBFOX1).</p>
<p>Thanks to this kind of research, there are now many new drugs in development and in clinical trials that could target one or more of the many brain-wide changes that occur with Alzheimer’s disease. Many researchers now believe that a more personalised approach to Alzheimer’s patients is the future.</p>
<p>This would involve a combination of drugs tailored to target several of the problems mentioned above, much like current treatments <a href="https://theconversation.com/how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">available for cancer</a>. The hope is that this innovative research will challenge and pioneer a new way of treating this complex disease.</p><img src="https://counter.theconversation.com/content/86799/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anna Cranston 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>New research is helping us understand exactly how Alzheimer’s works – and how to treat it.Anna Cranston, PhD Student in Neuroscience, University of AberdeenLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/758472017-06-01T20:13:50Z2017-06-01T20:13:50ZWhat causes Alzheimer’s disease? What we know, don’t know and suspect<figure><img src="https://images.theconversation.com/files/171067/original/file-20170525-23232-1rvtxjj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A hallmark of Alzheimer's disease is gradual deterioration of memory.</span> <span class="attribution"><a class="source" href="https://unsplash.com/search/memories?photo=7sPg5OLfExc">Roman Kraft/Unsplash</a></span></figcaption></figure><p><em>This is a long read.</em></p>
<hr>
<p>Alzheimer’s disease is the most common form of dementia, which is an <a href="https://www.fightdementia.org.au/about-dementia/what-is-dementia">umbrella term</a> used to describe general loss of memory, thinking skills and other day-to-day functions (such as cooking, paying bills, cleaning and even dressing). </p>
<p>A hallmark of <a href="https://www.fightdementia.org.au/about-dementia/types-of-dementia/alzheimers-disease">Alzheimer’s disease</a> is gradual deterioration of memory. But it is a biological disease, which means that, besides seeing outwards symptoms such as memory loss, we can also measure the breakdown that occurs in the brain as a consequence of disease progression.</p>
<p>Alzheimer’s is identified by the presence of two proteins in the brain, known as <a href="http://www.alz.org/braintour/plaques.asp">amyloid</a> and <a href="http://www.alz.org/braintour/tangles.asp">tau</a>. Amyloid proteins <a href="http://www.nature.com/nrm/journal/v15/n6/fig_tab/nrm3810_T1.html">aggregate into sticky clumps</a> called “plaques”. And tau proteins tend to form “tangles”. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=773&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=773&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=773&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=972&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=972&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171073/original/file-20170525-23234-2af3w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=972&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Dementia is an umbrella term used to describe general loss of memory, thinking skills and other day-to-day functions.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>While it is still unclear how amyloid and tau interact to cause the disease, these plaques and tangles seem to <a href="https://www.nia.nih.gov/alzheimers/publication/2011-2012-alzheimers-disease-progress-report/primer-alzheimers-disease-and">play a role in blocking messages</a> between brain cells. They induce inflammation wherever they accumulate, and may gum up the transportation system that helps clear the brain of debris.</p>
<p>Ultimately, the disease causes the death of brain cells. This results in an overall <a href="http://www.alzforum.org/news/research-news/brain-changes-speak-volumes-about-normal-aging-and-dementia">shrinking of brains</a> of patients with Alzheimer’s disease. Currently, while people can be diagnosed with <em>probable</em> Alzheimer’s disease, a <a href="http://www.alz.org/professionals_and_researchers_diagnosing_alzheimers.asp">reliable diagnosis</a> can only be made postmortem by searching for the tau and amyloid proteins. </p>
<p>Brain imaging techniques mean we can determine levels of these proteins in people who are still alive. However, while abnormal levels of the proteins in a healthy brain can increase the chances of developing Alzheimer’s disease, <a href="https://www.theatlantic.com/health/archive/2017/02/alzheimers-amyloid-hypothesis/517185/">this outcome is not always guaranteed</a>.</p>
<h2>Amyloid and tau</h2>
<p>Knowing the biology and mechanisms behind the genesis of Alzheimer’s disease is <a href="https://www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/">critical for the success</a> of future <a href="https://www.fightdementia.org.au/research/trials">clinical trials</a>. </p>
<p>The accumulation of amyloid protein in the brain is mainly found in Alzheimer’s disease, along with the way it spreads. Around 30% of healthy adults aged over 60 have high amyloid concentrations in their brain. It <a href="https://www.ncbi.nlm.nih.gov/pubmed/23477989">takes about 20 years</a> before people in this group start to display dementia symptoms such as memory loss. </p>
<p><a href="http://www.sciencemag.org/news/2016/05/tau-protein-not-amyloid-may-be-key-driver-alzheimer-s-symptoms">Tau</a>, on the other hand, is found across a wide range of conditions. These include Alzheimer’s disease, <a href="http://www.alz.org/dementia/chronic-traumatic-encephalopathy-cte-symptoms.asp">chronic traumatic encephalopathy</a> (a neurodegenerative disease linked to repetitive concussions and brain trauma), <a href="https://ghr.nlm.nih.gov/condition/niemann-pick-disease">Niemann-Pick</a> disease (a heritable disease that affects fat metabolism in cells) and <a href="http://www.alz.org/dementia/down-syndrome-alzheimers-symptoms.asp">Down Syndrome</a>. </p>
<p>Animal studies suggest a range of <a href="http://www.alzforum.org/news/research-news/more-evidence-distinct-tau-strains-may-cause-different-tauopathies">tau “strains”</a> exist, like “<a href="http://www.iflscience.com/health-and-medicine/new-prion-disease-raises-questions-about-whether-alzheimer-s-and-parkinson-s/">prions</a>”. Prions are small, infectious and <a href="http://memory.ucsf.edu/cjd/overview/prions">abnormally twisted (or misfolded) proteins</a> that can affect the brain by causing normally-functioning proteins to turn into diseased copies. </p>
<p>This, and the fact tau proteins are present across a range of conditions, makes it hard to determine the tau strains specific to Alzheimer’s disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171070/original/file-20170525-23245-1nbxqkg.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">The accumulation of amyloid protein in the brain is found in Alzheimer’s disease.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>We are <a href="http://www.alzforum.org/news/conference-coverage/next-generation-tau-pet-tracers-strut-their-stuff">still in the early stages</a> of studying tau in the brain. So far, <a href="https://www.newscientist.com/article/2082820-toxic-form-of-tau-protein-foils-memory-formation-in-alzheimers/">findings suggest</a> increased tau in memory-related areas of the brain is closely related to memory decline, even in healthy older adults.</p>
<p>But how amyloid plaques and tau tangles interact to influence the onset of Alzheimer’s disease remains a puzzle for researchers. Amyloid first begins to <a href="http://www.nationalacademies.org/hmd/%7E/media/353F303C759D406C8B893618DF9260F7.ashx">appear in the outer edges of the brain</a> (what we call the “cortex”), which is where higher-order cognitive functions are located. </p>
<p>Tau <a href="https://news.usc.edu/91957/researchers-pinpoint-brain-region-as-ground-zero-of-alzheimers-disease/">first appears deep in the brain</a>, very early in the areas of the brain stem related to sleep, arousal and vigilance, and subsequently in <a href="http://www.massgeneral.org/News/pressrelease.aspx?id=1861">memory centres</a> like the entorhinal cortex and hippocampus. </p>
<p>Interestingly, while high levels of amyloid plaques can be seen in healthy older adults, the plaques do not seem to affect cognitive function to the same degree as tau tangles. This has led some researchers to suggest that <a href="http://www.sciencemag.org/news/2016/05/tau-protein-not-amyloid-may-be-key-driver-alzheimer-s-symptoms">amyloid is necessary, but not sufficient by itself,</a> to result in dementia symptoms.</p>
<p>Another big question is which comes first, amyloid or tau? <a href="https://www.ncbi.nlm.nih.gov/pubmed/22002422">A seminal autopsy study</a> of 2,332 brains aged between ten and 90 years old showed tau appears as early as in people’s 20s and will keep accumulating across the lifespan, even in healthy people, until death. </p>
<p>One working hypothesis is that once amyloid appears on the scene, <a href="http://www.alzforum.org/news/research-news/brain-imaging-suggests-av-unleashes-deadly-side-tau">tau will accelerate its misfolding</a>, which will <a href="http://www.alzforum.org/news/conference-coverage/tau-pet-studies-agree-tangles-follow-amyloid-precede-atrophy">promote more amyloid and brain cell death</a>. A <a href="http://www.alzforum.org/news/conference-coverage/amyloid-and-neurodegeneration-have-different-underlying-genetics">commonly used analogy</a> is that tau represents the “gun” and amyloid the “bullet”.</p>
<h2>The role of genes</h2>
<p>So how does amyloid appear on the scene in the first place? <a href="http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/art-20046552">Genes</a> may play an important role. </p>
<p>If you inherit the Alzheimer’s disease gene from only one parent and still get the disease, it is known as <a href="http://www.dian-info.org/">dominantly inherited Alzheimer’s disease</a>, or familial or autosomal dominant Alzheimer’s disease. Here, <a href="http://www.alzforum.org/early-onset-familial-ad/overview/what-early-onset-familial-alzheimer-disease-efad">mutations in one of three genes</a> (amyloid precursor protein, presenilin 1 or presenilin 2) cause a rapid accumulation of amyloid in the brain. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=561&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=561&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=561&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=705&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=705&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171072/original/file-20170525-23232-1odlb05.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=705&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Familial Alzheimer’s disease results in severe loss of brain volume and memory at a devastatingly young age.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>This results in severe loss of brain volume and memory at a devastatingly young age (approximately 40 years old). Dominantly inherited Alzheimer’s disease is rare in the <a href="http://www.dian-info.org/institutions_Australia.htm">Australian population</a>, accounting for only 1% of all Alzheimer’s disease cases. </p>
<p>However, people who carry these mutations have a 99.9% chance of developing the disease, and a 50% chance of passing the mutations to their children.</p>
<p>Amyloid also accumulates with age. <a href="http://www.alz.org/alzheimers_disease_causes_risk_factors.asp">Age is the greatest risk factor</a> for sporadic Alzheimer’s disease (which accounts for 99% of Alzheimer’s disease cases). As the average age of onset for sporadic Alzheimer’s disease is 80, it is sometimes called late-onset Alzheimer’s disease. </p>
<p>The strongest genetic risk factor for sporadic Alzheimer’s disease is a gene called “<a href="https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet">apolipoprotein E (APOE) ε4</a>”, and emerging research suggests this increased risk may be due to inefficiencies in clearing amyloid from the brain. The ε4 gene is not itself predictive or diagnostic of Alzheimer’s disease. Only 40% of patients carry the ε4 gene, and many carriers do not develop the disease. </p>
<h2>Diet, diabetes and obesity</h2>
<p>Diet has long been seen as a <a href="https://www.thl.fi/fi/web/thlfi-en/research-and-expertwork/projects-and-programmes/finger-research-project">potential preventive factor</a> against dementia risk. However, the effects of dietary supplements (such as omega-III fatty acids) and adherence to specific diets (such as the <a href="http://www.alz.org/brain-health/adopt_healthy_diet.asp">Mediterranean diet</a>) <a href="http://www.cochrane.org/CD009002/DEMENTIA_omega-3-fatty-acids-treatment-dementia">have not been entirely convincing</a>. Evidence is yet to definitively show any particular diet or supplement has a substantial effect on reducing dementia risk or even memory decline.</p>
<p>Some evidence <a href="http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/diabetes-and-alzheimers/art-20046987">links type 2 diabetes</a> with risk of Alzheimer’s disease. But there is stronger support for an association between <a href="http://www.thelancet.com/journals/landia/article/PIIS2213-8587(15)00033-9/abstract">weight</a> (body mass index, or BMI) and dementia. </p>
<p>Higher BMI (over 40) is linked with greater risk of premature death and increased risk of dementia compared with people of normal weight. Evidence also suggests people with lower BMI (under 18) in midlife and beyond have a significantly increased risk of dementia compared to those in healthy ranges (18.5 to 25). </p>
<p>A recent paper suggests <a href="http://www.alzforum.org/news/research-news/no-being-thin-does-not-lead-alzheimers-disease">low BMI does not cause Alzheimer’s disease</a> but that lower BMI may arise as a result of brain changes, such as appetite suppression, that occur early due to the disease.</p>
<p>Some studies have also suggested Alzheimer’s disease can be known as <a href="http://www.newyorker.com/magazine/2017/04/03/is-fat-killing-you-or-is-sugar">“type 3” diabetes</a>, as patients show poorer energy consumption in the brain. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/">Some researchers suggest this is driven by insulin resistance</a>. However, this a controversial area of research and study results to this effect need independent replication.</p>
<h2>Physical activity</h2>
<p>Studies now suggest exercise <a href="http://www.health.harvard.edu/mind-and-mood/can-you-grow-new-brain-cells">can increase neuroplasticity</a> in the brain. Neuroplasticity refers to the brain’s ability to form new connections between nerve networks, particularly in memory centres.</p>
<p>Breaking a sweat may <a href="http://www.sciencemag.org/news/2013/10/how-exercise-beefs-brain">increase levels of a protein</a> called the brain-derived neurotrophic factor, which induces the growth and survival of brain cells. Just as protein shakes may help muscles grow after exercise, this protein may <a href="http://www.huffingtonpost.com/paul-spector-md/your-brain-the-new-users-_b_9608948.html">strengthen the brain’s ability</a> to cope with injury or disease, not just Alzheimer’s. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171074/original/file-20170526-23230-6dwe6.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">Exercise can help the brain repair nerve connections.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<h2>Sleep</h2>
<p>Sleep <a href="http://www.npr.org/sections/health-shots/2016/01/04/460620606/lack-of-deep-sleep-may-set-the-stage-for-alzheimers">problems are common</a> in patients with Alzheimer’s disease. It is likely brain regions that regulate sleep-wake cycles deteriorate, resulting in sleep disruptions. </p>
<p><a href="http://www.alzforum.org/news/research-news/sleep-and-brain-cleansing-fresh-insights-regulation-and-disruption">Animal studies</a> suggest disrupted sleep may result in increased amyloid accumulation. This is because a waste-draining system (known as the glymphatic system proposed to be involved in clearing amyloid from the brain) is <a href="http://www.cell.com/neuron/abstract/S0896-6273(17)30088-0">significantly more active</a> when people are asleep, and less effective during sleep disruption. </p>
<p>While research into the mechanisms behind sleep and amyloid clearance is still in the early stages, mounting evidence supports the idea sleep disturbances, or <a href="https://www.bumc.bu.edu/busm/2017/02/23/prolonged-sleep-may-predict-dementia-risk/">abnormal sleeping patterns</a>, may be an early <a href="https://www.researchgate.net/profile/Bryce_Mander/publication/304191436_Sleep_A_Novel_Mechanistic_Pathway_Biomarker_and_Treatment_Target_in_the_Pathology_of_Alzheimer's_Disease/links/5775841b08ae4645d60bad5e.pdf">indicator of Alzheimer’s disease</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=882&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=882&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=882&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1109&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1109&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171075/original/file-20170526-23230-id3l9a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1109&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sleep disturbance may be an early indicator of Alzheimer’s disease.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<h2>Mood</h2>
<p>Earlier-life depression has been associated with <a href="https://newoldage.blogs.nytimes.com/2013/05/01/does-depression-contribute-to-dementia/?_r=0">a doubled risk of developing dementia</a>. Recent <a href="http://www.neurology.org/content/88/4/371.short">evidence also suggests</a> anxiety, stress and elevated cortisol (stress-hormone) levels may play a role. </p>
<p>While the mechanisms explaining how mood might increase dementia risk remain unclear, <a href="http://www.nature.com/nrneurol/journal/v7/n6/abs/nrneurol.2011.60.html">studies suggest</a> symptoms of anxiety or depression may be associated with factors that increase your risk of vascular conditions such as heart disease and stroke. </p>
<p>They have also been associated with increasing levels of amyloid in the brain, and increased inflammation.</p>
<h2>Cognitive reserve or resilience</h2>
<p>Some people with high amyloid in their brains do not develop Alzheimer’s disease. It is suggested these people have “cognitive reserve”, which makes them able to <a href="https://academic.oup.com/brain/article/137/4/1167/371918/Compensatory-mechanisms-in-higher-educated">better compensate</a> for, or be more resilient to, increasing levels of disease in the brain. </p>
<p>This term “cognitive reserve” refers to any psychological and social factors (such as <a href="http://www.alzforum.org/news/research-news/cognitive-reserve-more-evidence-it-prevents-neurodegeneration">higher levels of education, occupational attainment or intelligence</a>) that could increase one’s chances of compensating for disease burden.</p>
<p>However, other research suggests individuals with cognitive reserve are also more likely to exhibit a <a href="http://www.neurology.org/content/75/11/990.short">sudden and precipitous drop</a> in memory performance at a later stage, unlike the “slow and steady” decline that is characteristic of most Alzheimer’s disease cases. As such, while cognitive reserve may be protective to a degree, it may simply delay disease onset.</p>
<h2>Preventing Alzheimer’s disease</h2>
<p>While a <a href="http://www.sciencemag.org/news/2017/02/another-alzheimers-drug-flops-pivotal-clinical-trial">cure continues to elude us</a>, many Alzheimer’s experts now realise <a href="http://news.harvard.edu/gazette/story/2017/04/harvard-researchers-plot-early-attack-against-alzheimers/">early diagnosis and intervention</a> is key to stopping the disease in its tracks. </p>
<p>If brain shrinkage has already begun, removing amyloid from the brain is unlikely to be effective. Recent <a href="http://www.sciencemag.org/news/2016/03/why-big-change-lilly-s-alzheimer-s-trial-not-evidence-its-drug-has-failed-again">clinical trials</a>, in which amyloid plaques were removed from the brains of Alzheimer’s disease patients, showed cognitive performance and clinical symptoms did not drastically improve over the course of the trial. </p>
<p>Clinical trials experts are <a href="http://www.tedmed.com/speakers/show?id=6607">turning their gaze</a> to earlier stages in the disease trajectory. For instance, <a href="https://www.florey.edu.au/alzheimers-disease">Australian researchers are recruiting participants</a> for a study that will test drugs that aim to remove amyloid in healthy older adults with high levels of amyloid plaques.</p>
<p>Additionally, we and other scientists are trying to understand factors that contribute to amyloid accumulation, so it can be stopped before it even starts. </p>
<p>This involves studying middle-aged adults, and following them over a long time to determine what combinations of genetic and environmental factors put people at risk of Alzheimer’s disease, or protect them against it. If you’d like to be a part of such a study in middle-aged Australians, you can head to the <a href="https://www.healthybrainproject.org.au/">Healthy Brain Project</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/171076/original/file-20170526-23260-6jor39.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">Engaging your brain can be helpful in reducing dementia risk.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>While the brain-training sector is worth millions of dollars annually, there is <a href="https://www.theatlantic.com/science/archive/2016/10/the-weak-evidence-behind-brain-training-games/502559/">no convincing evidence</a> that brain training (computerised programs aimed at improving your memory through games and puzzles) can <a href="https://www.scientificamerican.com/article/brain-training-doesn-t-make-you-smarter/">result in better cognitive abilities</a> in everyday life. </p>
<p>But maintaining physical, social and brain health is an <a href="https://www.theguardian.com/society/2015/mar/12/dancing-sudoku-fish-and-fruit-the-keys-to-a-mentally-alert-old-age">important component of reducing dementia risk</a>, which all Australians can implement in their daily lives. Learning a new language, picking up bridge, travelling and going back to study are ideal examples as they incorporate brain challenges and increase social engagement, which are both important for dynamically engaging the brain.</p><img src="https://counter.theconversation.com/content/75847/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yen Ying Lim receives funding from the National Health and Medical Research Council, the Australian Research Council, and the Alzheimer's Association. </span></em></p><p class="fine-print"><em><span>Rachel Buckley receives funding from the National Health and Medical Research Council, the Australian Research Council and the Brain Foundation. </span></em></p>Alzheimer’s disease is the most common form of dementia, but treatments are still far from successful in clinical trials. Here is what we know about the disease, and what is yet to be uncovered.Yen Ying Lim, Research Fellow, Florey Institute of Neuroscience and Mental HealthRachel Buckley, Research Fellow, Harvard Medical School, Research Fellow, Florey Institute of Neuroscience and Mental HealthLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/744602017-03-16T12:30:30Z2017-03-16T12:30:30ZThe brain: a radical rethink is needed to understand it<figure><img src="https://images.theconversation.com/files/161216/original/image-20170316-10925-148wlrp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Has neuroscience been on the wrong track for centuries?</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/31290193@N06/5621741844/in/photolist-5GhxMn-9hiPC-5UPJ7n-c27Be9-c27vR7-5Vi6z4-5Vi6FV-5Vnsx3-bpSxdB-7nBTuf-dYocn5-5VnsDf-mxeWUb-4uNsCX-6L4net-yBNSqL-6tgcSC-9yLTZw-9yHNe2-7kHkjn-bWEZpA-Fuz2cu">Justin Pickard/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Understanding the human brain is arguably the greatest challenge of modern science. The <a href="http://www.sciencemuseum.org.uk/broughttolife/people/paulbroca">leading approach</a> for most of the <a href="https://books.google.co.uk/books?id=020xAQAAIAAJ&printsec=frontcover&dq=how+to+read+character:+a+new+illustrated+hand-book&hl=en&sa=X&redir_esc=y#v=onepage&q=how%20to%20read%20character%3A%20a%20new%20illustrated%20hand-book&f=false">past 200 years</a> has been to link its functions to different brain regions or even individual neurons (brain cells). But recent research <a href="http://www.nature.com/nrn/journal/v10/n3/abs/nrn2575.html">increasingly suggests</a> that we may be taking completely the wrong path if we are to ever understand the human mind.</p>
<p>The idea that the brain is made up of numerous regions that perform specific tasks is known as “<a href="https://theconversation.com/how-our-modular-brain-pieces-the-world-together-58990">modularity</a>”. And, at first glance, it has been successful. For example, it can provide an explanation for how we recognise faces by activating a chain of specific brain regions in the <a href="http://brainmadesimple.com/occipital-lobe.html">occipital</a> and <a href="http://brainmadesimple.com/temporal-lobe.html">temporal lobes</a>. Bodies, however, are processed by a different set of brain regions. And scientists believe that yet other areas – memory regions – help combine these perceptual stimuli to create holistic representations of people. The activity of certain brain areas has also been <a href="https://theconversation.com/what-a-little-known-brain-region-can-tell-us-about-depression-60410">linked to specific conditions and diseases</a>.</p>
<p>The reason this approach has been so popular is partly due to technologies which are giving us unprecedented insight into the brain. <a href="https://theconversation.com/brain-scanners-allow-scientists-to-read-minds-could-they-now-enable-a-big-brother-future-72435">Functional magnetic resonance imaging (fMRI)</a>, which tracks changes in blood flow in the brain, allows scientists to see brain areas light up in response to activities – helping them map functions. Meanwhile, <a href="https://theconversation.com/exciting-cells-and-controlling-heartbeats-could-optogenetics-create-drug-free-treatments-56539">Optogenetics</a>, a technique that uses genetic modification of neurons so that their electrical activity can be controlled with light pulses – can help us to explore their specific contribution to brain function.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=374&fit=crop&dpr=1 600w, https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=374&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=374&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=470&fit=crop&dpr=1 754w, https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=470&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/160989/original/image-20170315-5360-gmac0r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=470&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">FMRI scan during working memory tasks.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:FMRI_scan_during_working_memory_tasks.jpg">John Graner/wikipedia</a></span>
</figcaption>
</figure>
<p>While both approaches generate <a href="https://www.sciencedaily.com/releases/2014/01/140106103741.htm">fascinating results</a>, it is not clear whether they will ever provide a meaningful understanding of the brain. A neuroscientist who finds a correlation between a neuron or brain region and a specific but in principle arbitrary physical parameter, such as pain, will be tempted to draw the conclusion that this neuron or this part of the brain controls pain. This is ironic because, even in the neuroscientist, the brain’s inherent function is to find correlations – in whatever task it performs.</p>
<p>But what if we instead considered the possibility that all brain functions are distributed across the brain and that all parts of the brain contribute to all functions? If that is the case, correlations found so far may be a perfect trap of the intellect. We then have to solve the problem of how the region or the neuron type with the specific function interacts with other parts of the brain to generate meaningful, integrated behaviour. So far, there is no general solution to this problem – just hypotheses in specific cases, such as for recognising people. </p>
<p>The problem can be illustrated by a recent study which found that the psychedelic drug LSD can <a href="https://theconversation.com/how-lsd-helped-us-probe-what-the-sense-of-self-looks-like-in-the-brain-57703">disrupt the modular organisation</a> that can explain vision. What’s more, the level of disorganisation is linked with the severity of the the “breakdown of the self” that people commonly experience when taking the drug. The study found that the drug affected the way that several brain regions were communicating with the rest of the brain, increasing their level of connectivity. So if we ever want to understand what our sense of self really is, we need to understand the underlying connectivity between brain regions as part of a complex network. </p>
<h2>A way forward?</h2>
<p>Some researchers <a href="https://www.scientificamerican.com/article/a-new-phrenology/">now believe</a> the brain and its diseases in general can only be understood as an <a href="http://www.nature.com/nrn/journal/v10/n3/abs/nrn2575.html">interplay between tremendous numbers of neurons distributed across the central nervous system</a>. The function of any one neuron is dependent on the functions of all the thousands of neurons it is connected to. These, in turn, are dependent on those of others. The same region or the same neuron may be used across a huge number of contexts, but have different specific functions depending on the context. </p>
<p>It may indeed be a tiny perturbation of these interplays between neurons that, through avalanche effects in the networks, causes conditions like depression or Parkinson’s disease. Either way, we need to understand the mechanisms of the networks in order to understand the causes and symptoms of these diseases. Without the full picture, we are not likely to be able to successfully cure these and many other conditions.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=661&fit=crop&dpr=1 600w, https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=661&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=661&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=831&fit=crop&dpr=1 754w, https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=831&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/160690/original/image-20170314-10745-ns2bxx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=831&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Map of neural connections.</span>
<span class="attribution"><span class="source">Thomas Schultz/wikimedia</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In particular, neuroscience needs to start investigating how network configurations arise from the brain’s lifelong attempts to make sense of the world. We also need to get a clear picture of how the cortex, brainstem and cerebellum interact together with the muscles and the tens of thousands of optical and mechanical sensors of our bodies to create one, integrated picture. </p>
<p>Connecting back to the physical reality is the only way to understand how information is represented in the brain. One of the reasons we have a nervous system in the first place is that the evolution of mobility required a controlling system. Cognitive, mental functions – and even thoughts – can be regarded as mechanisms that evolved in order <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619124/">to better plan for the consequences</a> of movement and actions.</p>
<p>So the way forward for neuroscience may be to focus more on general neural recordings (with optogenetics or fMRI) – without aiming to hold each neuron or brain region responsible for any particular function. This could be fed into theoretical network research, which has the potential to account for a variety of observations and provide an integrated functional explanation. In fact, such a theory should help us design experiments, rather than only the other way around.</p>
<h2>Major hurdles</h2>
<p>It won’t be easy though. Current technologies are expensive – there are major financial resources as well as national and international prestige invested in them. Another obstacle is that the human mind tends to prefer simpler solutions over complex explanations, even if the former can have limited power to explain findings.</p>
<p>The entire relationship between neuroscience and the pharmaceutical industry is also built on the modular model. Typical strategies when it comes to common neurological and psychiatric diseases are to identify one type of receptor in the brain that can be targeted with drugs to solve the whole problem.</p>
<p>For example, SSRIs – which block absorption of serotonin in the brain so that more is freely available – are currently used to treat a number of different mental health problems, including depression. But they don’t work for many patients and there may be a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/">placebo effect involved when they do</a>. </p>
<p>Similarly, epilepsy is today widely seen as a single disease and is <a href="http://www.nhs.uk/conditions/Epilepsy/Pages/Introduction.aspx">treated with anticonvulsant drugs</a>, which work by dampening the activity of <em>all</em> neurons. Such drugs don’t work for everyone either. Indeed, it could be that any minute perturbation of the circuits in the brain – arising from one of thousands of different triggers unique to each patient – could push the brain into an epileptic state.</p>
<p>In this way, neuroscience is gradually losing compass on its purported path towards understanding the brain. It’s absolutely crucial that we get it right. Not only could it be the key to understanding some of the biggest mysteries known to science – such as consciousness – it could also help treat a huge range of debilitating and costly health problems.</p><img src="https://counter.theconversation.com/content/74460/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Henrik Jörntell receives funding from the Swedish Research Council, Hjärnfonden, the EC-FP7 and NIH USA. </span></em></p>There’s both money and prestige invested in the simple idea that different brain areas are responsible for certain functions. But that doesn’t make it true.Henrik Jörntell, Senior Lecturer in Neuroscience, Lund UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/439412015-07-03T05:27:46Z2015-07-03T05:27:46ZSurvival of the fittest: how brain tumours adapt through complex ecosystems<figure><img src="https://images.theconversation.com/files/87151/original/image-20150702-11345-1wwhek5.png?ixlib=rb-1.1.0&rect=0%2C2%2C1914%2C1068&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Complex enough – without cancer.</span> <span class="attribution"><a class="source" href="https://vimeo.com/4834650">JonO</a></span></figcaption></figure><p>Despite advances in medical technology and a constantly evolving understanding of the mechanisms of cancer progression, researchers and clinicians are faced with a litany of challenges along the road to finding a cure for the most aggressive forms of cancer. This is particularly true of glioblastoma multiforme, the most common and most aggressive form of human brain cancer.</p>
<p>Glioblastoma is universally fatal. Some of the most destructive hallmarks of these tumours, such as uncontrolled and invasive growth into healthy tissues, make this form of brain cancer very difficult to treat. Left untreated people affected typically survive only a few months. The current gold standard for treatment is a combination of surgery, chemotherapy and radiation therapy, but this rarely extends the patients’ survival <a href="http://www.ncbi.nlm.nih.gov/pubmed/23291739">beyond two years</a> as more resistant tumours always grow back. The ability for cells to adapt, evolve and evade allows hardier tumour cells to develop defence mechanisms against conventional treatment.</p>
<h2>Cancer cells are as unique as snowflakes</h2>
<p>To understand how glioblastoma tumours can evolve to become more resistant, it’s important to recognise brain tumours not as uniform tissues, but as complex populations of diverse, dynamic and transforming cell types. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=601&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=601&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=601&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=755&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=755&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86735/original/image-20150629-9099-1j0iwyi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=755&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Glioblastoma multiforme.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Glioblastoma_multiforme_-_MRT_T2_ax.jpg#/media/File:Glioblastoma_multiforme_-_MRT_T1KM_sag.jpg">Hellerhof</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In healthy tissues, a coordinated system of molecules tightly regulates the rate of cell division and expression of genes in response to environmental cues. In cancer cells, this machinery becomes compromised and the cells begin dividing uncontrollably and build up genetic mutations. As the cells reproduce, the genetic identity of the offspring evolves with each new division.</p>
<p>We’re also finding more and more evidence that glioblastoma tumours are maintained by a small cache of <a href="https://theconversation.com/can-elusive-cancer-stem-cells-seed-new-tumours-months-after-chemotherapy-39553">cancer stem cells</a>. These are slowly dividing, hardy cells which are capable of transforming into many different cell types under the right conditions and rebuilding tumours with new cells of diverse genetic profile.</p>
<p>Many of these cell types possess traits for survival. Rapidly dividing cells can escape surgical treatment, for example, by growing and <a href="http://www.ncbi.nlm.nih.gov/pubmed/24946761">replicating deeper into the brain</a> where a more permissible environment allows for them to expand with fewer threats to their well-being. These escapee cells often diffuse across the brain by hijacking and migrating along the blood vessels. This invasion and migration places a buffer of healthy tissue between the tumour mass and the surgeon’s scalpel.</p>
<p>Surgery can also be resisted through a process known as angiogenesis, which is the production of new blood vessels signalled by tumour cells <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Tumor+vasculature+and+glioma+stem+cells%3A+Contributions+to+glioma+progression">to secure new nutrition supply lines</a>. Many cells within the tumour possess a toolbox of genes to signal for these new supplies.</p>
<p>Some brain tumour cells also express <a href="http://www.ncbi.nlm.nih.gov/pubmed/25943888">genes such as MGMT</a>, which grants the ability to repair chemotherapy-induced DNA damage and bypass programmed cell death. Considering that <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Individualdrugs/Temozolomide.aspx">temozolomide</a>, the current drug used to treat glioblastoma, works by damaging DNA through a process known as methylation, cells that are MGMT-positive can resist the drug’s effects. As easily exposed tumour cells and those which are sensitive to drugs and radiation are weeded out, cells with these survival traits are selected for expansion and can become the dominant cell type within a tumour mass.</p>
<h2>Tumours are rowdy ecosystems</h2>
<p>By comparing the tumour landscape to an ecosystem, we can apply an <a href="http://www.ncbi.nlm.nih.gov/pubmed/22258609">evolutionary model</a> of adaptability, environmental pressures and selection. In an ecosystem, numerous species of plant and animal life compete for limited resources, maintaining a dynamically shifting balance of power. If we interfere with one species, a competitor may inherit a greater share of the resources and have more room to spread out.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/87160/original/image-20150702-11342-kzd2j4.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">We’re used to thinking about environmental ecosystems, but cancer has one too.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/pierrepocs/5480153734/in/photolist-9mgdMd-7Efwg5-6HjAp2-s4HJr2-bvqRTg-oEHQYr-66Gp3z-avygEs-7LpQA4-8a8pg2-qPK44C-9jbGHn-8yxLyK-q8XuMQ-6a4pJr-8epuqf-qDr3FW-6xCw9d-rdqatK-rBA4Fm-qrJSv6-oHED9U-oZXJ2y-c69Db-rJMC2t-rmEdxU-sbFQ1q-oswrSq-swLB88-s4jTZb-qxYzqR-9jbGDk-r66H6h-rDtaiz-p2JbmZ-rD7XEE-q4VnRy-qojLca-6HobXC-rgaAsH-qJajKA-p5bE5S-nWsETB-q9TMdr-reTVRq-a2Uttk-rdb5zY-bEAzy6-oHGuyg-b9Wi6p">Pierre Pocs Photography</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>These principles can be applied to the tumour habitat, as different cancer cell types compete for space within the brain. Similarly, cells within a tumour ecosystem follow patterns resembling the Darwinian model of natural selection. Dividing cells may produce offspring with mutations that equip them with tools to promote the production of new blood vessels and divide more rapidly. This grants them a competitive edge to secure resources and successfully reproduce.</p>
<h2>Next generation treatments</h2>
<p>An updated understanding of the brain cancer environment may promote the discovery of nuanced treatment options in the future. One such strategy would be to minimise tumour evolution by keeping cells in a slowly dividing and treatment-responsive state rather than targeting them for general eradication. For this strategy to be realised, clinical researchers could investigate new ways to halt glioblastoma progression by homing in on, and tampering with, the machinery which allows tumour cells to adapt in their ecosystem.</p>
<p>A <a href="http://www.ncbi.nlm.nih.gov/pubmed/25759023">recent study</a> used computer models of genome maps from the <a href="http://cancergenome.nih.gov/">Cancer Genome Atlas Project</a> to identify targets such as ERBB2 or EGFR for which cancer drugs or treatments are already currently available or undergoing clinical trials. Many of these targets are well known in cancer research as tools exploited by tumour cells to develop a competitive advantage. </p>
<p>Focusing on these targets may present an opportunity to block the signalling capabilities for more aggressive traits without killing the cells and providing more space for a challenger. This would essentially de-fang a portion of tumour cells without seriously unbalancing the ecosystem.</p>
<p>A number of exciting developments have been made in the area of <a href="https://theconversation.com/uk/topics/cancer-immunotherapy">immunotherapy</a> and <a href="https://theconversation.com/uk/topics/personalised-medicines">personalised medicine</a> through whole-genome sequencing, but this technology is very much in its infancy. A strategy in which the glioblastoma cell population is kept lazy and placated rather than rowdy and competitive may complement current treatments to improve the quality of life for patients. Such an approach could buy patients a few more years while we develop and refine the next generation of treatment.</p><img src="https://counter.theconversation.com/content/43941/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Darren Ó hAilín 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>By tampering with the machinery which allows aggressive cancer cells to adapt, we can disrupt their ecosystem.Darren Ó hAilín, PhD candidate in Molecular Medicine, University of FreiburgLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/407792015-05-18T05:17:05Z2015-05-18T05:17:05ZWhat rats in a maze can teach us about our sense of direction<figure><img src="https://images.theconversation.com/files/81542/original/image-20150513-2487-1gdg01j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Just ask a cab driver - they've got that map in their head.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/bevgoodwin/8863849594/in/photolist-evgxF1-79XgbD-7a244Y-79Xgdc-7a2453-7a245b-p7xdcb-oTg9kT-91YrYa-f7ysQW-6MRRx-7a1mmb-3hy9ES-4mdd8V-7a1PTo-79X52V-7a244U-3bK5Yu-oti1kT-3Z1Ghe-7bL5x7-8gb87n-79WJRt-pTRRc4-79WJQX-7a1PTJ-bXf6wS-b9EWFB-6qkS7R-7a1PT5-3KvEEo-6TMipB-9zMndj-79X534-4mhfbu-9SqKY2-4mhfqY-4mdeAK-4mheB1-79WRUV-79WDxp-77tnDK-bXagnj-bJvhv-7a244S-ayz6xk-dL4CUv-6aCU2-4md7Hk-79X52X">Beverley Goodwin/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>London’s taxi drivers have to pass an exam in which they are asked to name the shortest route between any two places within six miles of Charing Cross – an area with more than 60,000 roads. We <a href="http://www.pnas.org/content/97/8/4398.full.pdf">know from brain scans</a> that learning “the knowledge” – as the drivers call it - increases the size of their hippocampi, the part of the brain crucial to spatial memory. </p>
<p>Now, new research suggests that bigger hippocampi may not be the only neurological benefit of driving a black cab. While the average person likely has many separate mental maps for different areas of London, the hours cabbies spend navigating may result in the joining of these maps into a single, global map. </p>
<h2>The grid-cell revolution</h2>
<p>Decades of work in both humans and animals has led to great leaps in our understanding of how the hippocampus and nearby brain regions form maps of space. A <a href="http://www.sciencedirect.com/science/article/pii/0006899371903581">key breakthrough</a> was made by John O’Keefe in the 1970s, who used electrodes to record the activity of individual brain cells in the hippocampus of rats as they walked around. He found cells that were active at single locations in space and named them place cells. For example, one cell was active when the rat was at the top left corner of the room, while others were active when the was rat in the middle of the room. </p>
<p>Four decades later, the same technique was used to <a href="http://www.nature.com/nature/journal/v436/n7052/abs/nature03721.html">identify so-called grid cells</a>. Like place cells, grid cells are active at specific points in space, but unlike place cells become active at multiple points organised in a repeating triangular pattern. Together, these cells and others are thought to be the cellular basis of the brain’s spatial map, and their discovery <a href="https://theconversation.com/nobel-prize-in-medicine-decades-of-work-on-the-brains-gps-recognised-32580">led to the award of a Nobel Prize in 2014</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/i9GiLBXWAHI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A grid cell’s activity as a rat moves around a room.</span></figcaption>
</figure>
<p>The repetitive pattern of grid cells means that they are activated in regular intervals as an animal explores an environment. It is thought that this repetitive activity can act like a ruler: by counting the number of times groups of grid cells become active, the rat’s brain can calculate how far it has moved. Conversely, these cells could also be used to navigate between points in space by calculating how far you have to move to reach a goal. If grid cells did act as a ruler, to get consistent measurements, the distance between the points where the cells are active would need to be the same no matter where you are.</p>
<p>Yet this requirement has been questioned by recent findings showing that in certain places grid cell activity is distorted from its regular pattern. For example, <a href="http://www.nature.com/nature/journal/v518/n7538/full/nature14153.html">the pattern is misshapen</a> near to the walls of some environments, being particularly strongly affected in the corners of triangular spaces. It is therefore difficult to use the grid cells as a ruler in these places. </p>
<h2>In the dark</h2>
<p>To investigate this issue, we recorded grid cells in rats exploring two compartments connected by a corridor. Crucially, the two compartments were identical: they looked, smelled and felt the same. We hypothesised that if grid cells do act as a useful measure of space their activity should span the two compartments even though they are perceptually identical, reflecting the fact that each has a different position in space.</p>
<p>A number of unglamorous months were spent in a dark room scattering rice around the compartments to encourage the rats to explore, followed by the only slightly more glamorous analysis of the data. Happily, we observed a number of interesting results. When the rats first started to explore, the activity patterns of the grid cells were identical in the two compartments, reflecting the identical sensory cues in each. </p>
<p>However, once the rats had spent a number of days exploring, the grid cells’ activity became more regular, eventually forming a single continuous pattern spanning both compartments. The grid cells had moved from having two separate and identical maps for each compartment to a single and continuous map covering both. Placing both compartments on the same map means that the grid cells can be used as a measure of space and for navigation between them. </p>
<p>While an interesting development, this will certainly not be the final word on the function of grid cells. Other studies have found apparently permanent distortions in their activity patterns, and it remains to be seen whether there are certain factors that prevent the regular pattern forming, and what they may be. Crucial future steps will likely include identifying how distortions in grid cell activity patterns relate to inaccuracies in navigation, and whether inactivating grid cells prevents accurate navigation. </p>
<p>Most studies use rodents to investigate the brain’s representation of space, as recording from single cells in humans currently requires invasive surgery. Brain scans have shown that <a href="http://www.nature.com/nature/journal/v463/n7281/abs/nature08704.html">humans also have grid cells</a>, but new technologies are needed before we can ask whether the grid cells of cab drivers form the same global patterns seen in our rats.</p><img src="https://counter.theconversation.com/content/40779/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Francis Carpenter receives funding from the Wellcome Trust.</span></em></p><p class="fine-print"><em><span>Caswell Barry receives funding from Wellcome Trust, Royal Society, and UCL.</span></em></p>When we figure out how places connect geographically, local maps in the brain join into a single, overarching map.Francis Carpenter, PhD student in neuroscience, UCLCaswell Barry, Sir Henry Dale Fellow in Cell & Developmental Biology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/240852014-03-12T06:37:16Z2014-03-12T06:37:16ZChattering brain cells hold the key to the language of the mind<figure><img src="https://images.theconversation.com/files/43603/original/f86qz8qt-1394548042.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Shhhh ...</span> <span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Culture_of_rat_brain_cells_stained_with_antibody_to_MAP2_(green),_Neurofilament_(red)_and_DNA_(blue).jpg">Gerry Shaw</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Let’s say Martians land on the Earth and wish to understand more about humans. Someone hands them a copy of the Complete Works of Shakespeare and says: “When you understand what’s in there, you will understand everything important about us.” </p>
<p>The Martians set to work – they allocate vast resources to recording every detail of this great tome until eventually they know where every “e”, every “a”, every “t” is on every page. They remain puzzled, and return to Earth. “We have completely characterised this book,” they say, “but we still aren’t sure we really understand you people at all.”</p>
<p>The problem is that characterising a language is not the same as understanding it, and this is the problem faced by brain researchers too. Neurons (brain cells) use language of a kind, a “code”, to communicate with each other, and we can tap into that code by listening to their “chatter” as they fire off tiny bursts of electricity (nerve impulses). We can record this chatter and document all its properties. </p>
<p>We can also determine the location of every single neuron and all of its connections and its chemical messengers. Having done this, though, we still will not understand how the brain works. To understand a code we need to anchor that code to the real world.</p>
<h2>Place, memory and administration</h2>
<p>We easily anchor Shakespeare’s code (we find out that “Juliet” refers to a specific young woman, “Romeo” to a specific young man) but can we do this for the brain? It seems we can. By recording the chatter of neurons while animals (and sometimes humans) perform the tasks of daily life, researchers have discovered that there are regions where the neural code relates to the real world in remarkably straightforward ways. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=455&fit=crop&dpr=1 600w, https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=455&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=455&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=572&fit=crop&dpr=1 754w, https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=572&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/43604/original/p3sk24w5-1394548457.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=572&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 sense of place, located.</span>
<span class="attribution"><a class="source" href="http://en.wikipedia.org/wiki/File:Gray739-emphasizing-hippocampus.png">Gray's anatomy</a></span>
</figcaption>
</figure>
<p>The best known of these is the code for “place”, discovered in a small and deeply buried part of the brain called the <a href="http://neuroscience.uth.tmc.edu/s4/chapter05.html">hippocampus</a>. A given hippocampal neuron starts chattering furiously whenever its owner (rat, mouse, bat, human) goes to a particular place. Each neuron tends to be most excited at a particular place (near the door, halfway along a wall) and so a large collection of neurons can, between them, be ready to “speak up” for any place in the environment. It is as if these neurons encode space, to form something akin to a mental map. </p>
<p>To determine where you are, you simply consult your hippocampus and see which neuron is active. (In practice, of course, many neurons will be active in that place and not just one – otherwise every time a neuron died you would lose a small piece of your map.) These neurons in the hippocampus are called “place neurons”, and are remarkable entities that form the foundation not only for our mental map of the space around us, but also for memories of the events that occur in that space – a kind of biographical record. Their importance is evident in the terrible disorientation and amnesia that result from their degeneration in Alzheimer’s disease. When the brain loses its link to its place in the world, and to its past, its owner loses all sense of self.</p>
<p>There are many other neurons in the brain whose code seems decipherable. Neurons that activate when facing a particular direction, or near a wall, or when you see your grandmother … Gradually we are piecing together the network of nodes in the brain that connect the inner code to the world outside.</p>
<p>This is not all that neurons do, of course. Much of the brain is involved with internal “administration”. For example, a large part of the <a href="http://neurolex.org/wiki/Nlx_anat_20090601">frontal lobe</a> (the brain behind the forehead) is involved in making decisions – how to prioritise activities, what to do next, and so on. Many neurons, scattered throughout the brain, have housekeeping duties to do with maintaining the code, improving and refining it, preserving the relevant parts as memory and discarding the rest.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=347&fit=crop&dpr=1 600w, https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=347&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=347&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=436&fit=crop&dpr=1 754w, https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=436&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/43605/original/wwnvk85t-1394548744.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=436&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Admin centre.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Gray726_frontal_lobe.png">Gray, vectorised by Mysid, coloured by was_a_bee.</a></span>
</figcaption>
</figure>
<p>Some of the most numerous neurons seem simply to have the job of suppressing their neighbours, so that the neural conversation, as it were, does not degenerate into the equivalent of uncontrollable shouting (which, in technical terms, we recognise as epilepsy).</p>
<h2>Still room for psychology</h2>
<p>It is clear that to understand the brain we need to investigate all aspects of its functioning, not just those that relate to internal administration but also those that connect to the outside world. </p>
<p>We need to determine how brain activity relates to what the brain’s owner is thinking, feeling and doing with respect to the world outside that brain – that is, we need to anchor the code to the real world. </p>
<p>For this, we need scientists who study thoughts, feelings and behaviour – psychologists – as much as we need those who study anatomy and physiology. Study of the brain requires investigation at all levels – otherwise, we will have a complete characterisation, but no understanding, of this remarkable organ.</p>
<p><em>Decoding the brain, a special report produced in <a href="http://www.danacentre.org.uk/events/2014/03/12/724">collaboration with the Dana Centre</a>, looks at how technology and person-to-person analysis will shape the future of brain research. Click here to read more Conversation UK articles on <a href="https://theconversation.com/brain-scans-are-fascinating-but-behaviour-tells-us-more-about-the-mind-24151">why behaviour tells us more about the brain than scans</a> and <a href="https://theconversation.com/unpicking-the-autism-puzzle-by-linking-empathy-to-reward-24050">linking empathy to reward</a> in autism.</em></p><img src="https://counter.theconversation.com/content/24085/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>I receive, or have received, funding for my work from the BBSRC, MRC, Wellcome trust and European Commission FP7
I am non-shareholding director of the biomedical instrumentation company Axona Ltd, which makes data acquisition systems for in vivo electrophysiological recording
</span></em></p>Let’s say Martians land on the Earth and wish to understand more about humans. Someone hands them a copy of the Complete Works of Shakespeare and says: “When you understand what’s in there, you will understand…Kate Jeffery, Director of the Institute of Behavioural Neuroscience, UCLLicensed as Creative Commons – attribution, no derivatives.