Neuroscience thinks big (and collaboratively)

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<ul><li><p>7/29/2019 Neuroscience thinks big (and collaboratively)</p><p> 1/6</p><p>What are the (long-term) goals of theseprojects? Why is now the right time to</p><p>invest in them?</p><p>Eric R. Kandel. The long-term goal ofthese highly ambitious projects is to gaina better understanding of the anatomical,molecular and circuit bases for the logicaloperations carried out by the human brain.The Human Brain Project (see Human BrainProject), based in Europe and led by H.M.,aims to understand the human brain bysimulating its functions through the useof supercomputers. The Brain Activity Map,with which I am more familiar, will be basedin the United States and coordinated byFrancis Collins, Director of the US NationalInstitutes of Health (NIH), and StoryLandis and Tom Insel, Directors of the USNational Institute of Neurological Disorders</p><p>and Stroke (NINDS) and the US NationalInstitute of Mental Health (NIMH),respectively.</p><p>These projects may be early for thehuman brain, but it is a good time toundertake these ambitious tasks in experi-mental animals for two reasons. First, inboth simple invertebrate animals, such asworms and flies, and in vertebrates, wehave begun to understand how the brainprocesses sensory information and howthe brain initiates movements. We havealso gained insight into the neural basis</p><p>of learning, memory, emotion and evendecision-making. These findings positionscientists, especially in the Brain ActivityMap project, to be able to begin to tacklethe overall organization of brain structureand function.</p><p>Second, in recent years, scientists havedeveloped a range of new technological,molecular and computational tools thatallow for more efficient and accurate record-ing from many nerve cells at the sametime, for mapping of connections betweenneurons in the brain, for correlating struc-ture and neural activity with function andfor manipulating neural activity to test thecausal role of defined neuronal elements inbehaviour.</p><p>Henry Markram. The Human Brain Projectis building the foundations that we need to</p><p>reconstruct and simulate the human brainand its diseases, and to develop related com-puting technologies. This is terribly urgent.Today, we are failing to translate our rapidlyimproving knowledge of the brain into ben-efits for society. Very soon the cost of braindisease will reach 10% of the worlds grossdomestic product (GDP), yet the develop-ment of new treatments is grinding to ahalt. There is still a massive gap between theneuroscience laboratory and the clinic. Inthe same way, we still do not know how touse our knowledge about the brain to build</p><p>new computing technologies. Neuroscienceis like the infant brain it is flooded withdata and theories but lacks the ability tobring them together in a unified view. Wepin our hopes on more and more data with-out realizing that experiments can only giveus a small fraction of what we need. Theattempt to reconstruct the human brain asa computer model can provide a new focusfor neuroscience and for clinical and tech-nological research. It will help us to cleanup conflicting reports and teach us howto apply knowledge from animal studies tounderstanding the human brain. Ultimately,it will allow us to discover the fundamentalprinciples governing brain structure andfunction and to predictively reconstructthe brain from fragments of experimentaldata. Without this kind of understanding,we will continue to struggle to develop newtreatments and brain-inspired computing</p><p>technologies.</p><p>Paul M. Matthews. The Human BrainProject will engage a consortium of 80 neu-roscience centres across Europe to aggregatebrain functional data on an unprecedentedscale, use data-mining techniques to derivean understanding of the way the humanbrain is constructed and then apply what islearned to revolutionize computing and todevelop new approaches for the diagnosisand treatment of brain disease. This is ahugely ambitious remit. A strength of thisproject is the focus on multilevel integra-tion. However, at this early stage, the projectis more aspirational than scientifically welltargeted. It emphasizes a massive scaling upof activities in many areas of neurosciencerather than exhaustively exploring a specificquestion or innovation challenge.</p><p>The BRAIN Initiative (Brain Researchthrough Advancing InnovativeNeurotechnologies Initiative; see BRAINInitiative) is still more of a commitmentthan a reality. The specific goals are notset but will be considered over 2013 by anadvisory committee to the US NIH Director.</p><p>However, a vision for the BRAIN Initiative,which focused attention on the challengeof developing tools able to describe activ-ity across every cell in a functional unit tocharacterize emergent properties, was setout in a 2012 Neuron paper1 from a groupled by R.Y. Specific opportunities offered by</p><p>voltage-sensitive optogenetic probes, wire-less (nano) electrophysiological sensors andsynthetic biology were highlighted.</p><p>Why are these initiatives coming now?Politically, we need them to help real sci-ence funding grow. They both emphasize</p><p>VIEWPOINT</p><p>Neuroscience thinks big(and collaboratively)</p><p>Eric R. Kandel, Henry Markram, Paul M. Matthews, Rafael Yuste andChristof Koch</p><p>Abstract | Despite cash-strapped times for research, several ambitious collaborative</p><p>neuroscience projects have attracted large amounts of funding and media</p><p>attention. In Europe, the Human Brain Project aims to develop a large-scale</p><p>computer simulation of the brain, whereas in the United States, the Brain Activity</p><p>Map is working towards establishing a functional connectome of the entire brain,</p><p>and the Allen Institute for Brain Science has embarked upon a 10-year project to</p><p>understand the mouse visual cortex (the MindScope project). US President Barack</p><p>Obamas announcement of the BRAIN Initiative (Brain Research through Advancing</p><p>Innovative Neurotechnologies Initiative) in April 2013 highlights the political</p><p>commitment to neuroscience and is expected to further foster interdisciplinarycollaborations, accelerate the development of new technologies and thus fuel</p><p>much needed medical advances. In this Viewpoint article, five prominent</p><p>neuroscientists explain the aims of the projects and how they are addressing some</p><p>of the questions (and criticisms) that have arisen.</p><p>P E R S P E C T I V E S</p><p>NATURE REVIEWS |NEUROSCIENCE VOLUME 14 | SEPTEMBER 2013 |659</p><p> 2013 Macmillan Publishers Limited. All rights reserved</p></li><li><p>7/29/2019 Neuroscience thinks big (and collaboratively)</p><p> 2/6</p><p>how neuroscience can be an exciting area ofblue skies discovery research and an engineof economic recovery. We also need themto change the way we do neuroscience. Thebig problems of the brain demand inter-disciplinary approaches. There is so muchin the present system that creates barriersbetween investigators and institutions andthat slows (or even impedes) free flow ofinformation. We need examples that showhow to change this.</p><p>Rafael Yuste. The BRAIN Initiative willpromote the development of novel tech-nological platforms for neuroscience. Theexact focus is being decided by the threefunding agencies involved and their panels ofexperts and will become clear in a coupleof months. I expect it will focus on technol-ogies to perform systematic measurementsand manipulations of the activity of largenumbers of neurons in animal models andin human patients.</p><p>The time is ripe now because of thedevelopment of different areas of associatedtechnologies, such as optogenetics, syntheticbiology, nanotechnologies, microelectronicsand computational analysis of large-scaledatasets.</p><p>Christof Koch. To understand the cer-ebral cortex, we must bring all availableexperimental, computational and theoreti-cal approaches to focus on a single modelsystem. In particular, it is of the essence tomove from correlation this neuron orbrain region is active whenever the subjectdoes this or that to causation this setof molecularly defined neuronal popula-tions is causally involved in that behaviour.The power of optogenetics has given usunprecedented power to rapidly, specifically,delicately and reversibly turn specific con-nections or groups of neurons on and off.</p><p>The time is ripe for a concerted project com-bining these precise tools with large high-quality genomic and cellular databases andatlases, multiple physiological observatoriesto track the spiking activity of large ensem-bles of neurons in behaving animals underhighly standardized conditions, and anatom-ically and biophysically accurate computersimulations and theoretical studies.</p><p>What are the challenges facing theseprojects? Are there lessons to be learned</p><p>from other large-scale biology projects (theHuman Genome Project, for example)?</p><p>E.R.K. There are enormous challenges facingthese projects because the human brain is socomplex. These projects are unlike anythingundertaken before. It therefore is essentialthat we first study the terrain to be coveredand begin with more tractable goals forexample, understanding the logic of theworm and the fly brain, and understandingsensory, motor and cognitive systems in themammalian brain. In parallel, we need toimprove imaging capabilities for the humanbrain and to develop more precise meth-</p><p>odologies for measuring neural activity inhumans. What I gather is being planned forthe BRAIN Initiative, which has a superbadvisory committee, is a series of studygroups to outline the tasks to undertake andthe sequence in which to undertake them.</p><p>As I indicated, there are no precedentsfor this. The Human Genome Project wasimportant and successfully executed, but itwas much simpler. We knew exactly whatthe end point was. We needed to obtain thewhole sequence of nucleotides that makes upthe human genome. Further, we knew how</p><p>The contributors</p><p>Eric R. Kandel is University Professor at Columbia University, New York, USA, Fred Kavli Professor</p><p>and Director at the Kavli Institute for Brain Science at Columbia University and a senior</p><p>investigator at the Howard Hughes Medical Institute. A graduate of Harvard College, Cambridge,</p><p>Massachusetts, USA, and New York University School of Medicine, New York, USA, he trained in</p><p>neurobiology at the US National Institutes of Health, Bethesda, Maryland, USA, and in psychiatry at</p><p>Harvard Medical School. He joined the faculty of the College of Physicians and Surgeons at</p><p>Columbia University in 1974 as the founding director of the Center for Neurobiology and Behavior.</p><p>His research has been concerned with the molecular mechanisms of memory storage inAplysia</p><p>californica and mice. More recently, he has studied mouse models of memory disorders and mental</p><p>illness. Kandels work has been recognized with the Albert Lasker Award, the Heineken Award of</p><p>the Netherlands, the Gairdner Award of Canada, the Harvey Prize and the Wolf Prize of Israel, the</p><p>National Medal of Science USA and, in 2000, the Nobel Prize for Physiology or Medicine.</p><p>Henry Markram is Professor of Neuroscience at the Ecole Polytechnique Fdrale de Lausanne,</p><p>Switzerland. He researches the principles of neuronal and synaptic organization of the</p><p>neocortex, with the aim of understanding brain diseases. He discovered a series of principles of</p><p>synaptic transmission and plasticity and codeveloped the intense world theory of autism and</p><p>the theory of liquid computing. He has also initiated simulationbased neuroscience as a</p><p>national research programme in Switzerland and theHuman Brain Projectas a European plan</p><p>towards an integrated view of the brain.</p><p>Paul M. Matthews is Professor of Clinical Neurosciences and Head of the new Division of Brain</p><p>Sciences at Imperial College London, UK. He is also Vice President for Integrated Medicines</p><p>Development in the Neurosciences Unit and a Medicine Development Lead at GlaxoSmithKline,</p><p>Brentford, UK. His research interests include molecular and functional neuroimaging and in</p><p>neurological therapeutics development. Among other activities, he is Chair of the Imaging</p><p>Enhancement Working Group for UK Biobank, which intends to phenotype 100,000 people in the</p><p>longitudinal cohort study using advanced imaging of the brain, heart, carotids, bones and body,</p><p>and is leading the UK OPTIMISE Consortium for Stratified Medicine in Multiple Sclerosis. Paul M.</p><p>Matthews homepage:</p><p>brainsciences/</p><p>Rafael Yuste is Professor of Biological Sciences and Neuroscience at Columbia University, New</p><p>York, USA. He obtained his M.D. at the Universidad Autnoma in Madrid, Spain, worked in Sydney</p><p>Brenners laboratory at the MRC Laboratory of Molecular Biology in Cambridge, UK, carried out his</p><p>Ph.D. studies with Larry Katz in Torsten Wiesels laboratory at Rockefeller University, New York,</p><p>USA, and was a postdoctoral student of David Tank at AT&amp;T Bell Laboratories, Murray Hill, NewJersey, USA. In 1996, he joined the Department of Biological Sciences at Columbia University. In</p><p>2005, he became a Howard Hughes Medical Institute investigator and a codirector of the Kavli</p><p>Institute for Brain Circuits at Columbia University. He has pioneered the application of optical</p><p>imaging techniques to study the structure and function of the cortex, and he first proposed,</p><p>together with a group of colleagues, the Brain Activity Map1,3. Rafael Yustes homepage:http://</p><p></p><p>Christof Koch is Chief Scientific Officer at the Allen Institute for Brain Science in Seattle,</p><p>Washington, USA. He studied physics and philosophy at the University of Tbingen in Germany and</p><p>was awarded his Ph.D. in biophysics. In 1986, he joined the California Institute of Technology,</p><p>Pasadena, USA, as a Professor of Biology and Engineering, where he remained until 2013. He has</p><p>authored more than 300 scientific papers, patents and books on the biophysics of nerve cells, and</p><p>the neuronal and computational bases of visual perception, attention and, together with Francis</p><p>Crick, of consciousness. Christof Kochs homepage:</p><p>P E R S P E C T I V E S</p><p>660 | SEPTEMBER 2013 | VOLUME 14</p><p> 2013 Macmillan Publishers Limited. All rights reserved</p></li></ul>