Plasticité neuronale

Henry Markram started a dual scientific and medical career at the University of Cape Town, in South Africa. His scientific work in the 80’s revealed the polymodal receptive fields of pontomedullary reticular formation neurons in vivo and how acetylcholine re-organized these sensory maps. He moved to Israel in 1988 and obtained his PhD at the Weizmann Institute where he discovered a link between acetylcholine and memory mechanisms by being the first to show that acetylcholine modulates the NMDA receptor in vitro studies, and thereby gates which synapses can undergo synaptic plasticity. He was also the first to characterize the electrical and anatomical properties of the cholinergic neurons in the medial septum diagonal band. He carried out a first postdoctoral study as a Fulbright Scholar at the NIH, on the biophysics of ion channels on synaptic vesicles using sub-fractionation methods to isolate synaptic vesicles and patch-clamp recordings to characterize the ion channels. He carried out a second postdoctoral study at the Max Planck Institute, as a Minerva Fellow, where he discovered that individual action potentials propagating back into dendrites also cause pulsed influx of Ca2 into the dendrites and found that sub-threshold activity could also activated a low threshold Ca2 channel. He developed a model to show how different types of electrical activities can divert Ca2 to activate different intracellular targets depending on the speed of Ca2 influx – an insight that helps explain how Ca2 acts as a universal second messenger. His most well known discovery is that of the millisecond watershed to judge the relevance of communication between neurons marked by the back-propagating action potential. This phenomenon is now called Spike Timing Dependent Plasticity (STDP), which many laboratories around the world have subsequently found in multiple brain regions and many theoreticians have incorporated as a learning rule. At the Max-Planck he also started exploring the micro-anatomical and physiological principles of the different neurons of the neocortex and of the mono-synaptic connections that they form - the first step towards a systematic reverse engineering of the neocortical microcircuitry to derive the blue prints of the cortical column in a manner that would allow computer model reconstruction. He received a tenure track position at the Weizmann Institute where he continued the reverse engineering studies and also discovered a number of core principles of the structural and functional organization such as differential signaling onto different neurons, models of dynamic synapses with Misha Tsodyks, the computational functions of dynamic synapses, and how GABAergic neurons map onto interneurons and pyramidal neurons. A major contribution during this period was his discovery of Redistribution of Synaptic Efficacy (RSE), where he showed that co-activation of neurons does not only alter synaptic strength, but also the dynamics of transmission. At the Weizmann, he also found the “tabula rasa principle” which governs the random structural connectivity between pyramidal neurons and a non-random functional connectivity due to target selection. Markram also developed a novel computation framework with Wolfgang Maass to account for the impact of multiple time constants in neurons and synapses on information processing called liquid computing or high entropy computing. In 2002, he was appointed Full professor at the EPFL where he founded and directed the Brain Mind Institute. During this time Markram continued his reverse engineering approaches and developed a series of new technologies to allow large-scale multi-neuron patch-clamp studies. Markram’s lab discovered a novel microcircuit plasticity phenomenon where connections are formed and eliminated in a Darwinian manner as apposed to where synapses are strengthening or weakened as found for LTP. This was the first demonstration that neural circuits are constantly being re-wired and excitation can boost the rate of re-wiring. At the EPFL he also completed the much of the reverse engineering studies on the neocortical microcircuitry, revealing deeper insight into the circuit design and built databases of the “blue-print” of the cortical column. In 2005 he used these databases to launched the Blue Brain Project. The BBP used IBM’s most advanced supercomputers to reconstruct a detailed computer model of the neocortical column composed of 10’000 neurons, more than 340 different types of neurons distributed according to a layer-based recipe of composition and interconnected with 30 million synapses (6 different types) according to synaptic mapping recipes. The Blue Brain team built dozens of applications that now allow automated reconstruction, simulation, visualization, analysis and calibration of detailed microcircuits. This Proof of Concept completed, Markram’s lab has now set the agenda towards whole brain and molecular modeling. With an in depth understanding of the neocortical microcircuit, Markram set a path to determine how the neocortex changes in Autism. He found hyper-reactivity due to hyper-connectivity in the circuitry and hyper-plasticity due to hyper-NMDA expression. Similar findings in the Amygdala together with behavioral evidence that the animal model of autism expressed hyper-fear led to the novel theory of Autism called the “Intense World Syndrome” proposed by Henry and Kamila Markram. The Intense World Syndrome claims that the brain of an Autist is hyper-sensitive and hyper-plastic which renders the world painfully intense and the brain overly autonomous. The theory is acquiring rapid recognition and many new studies have extended the findings to other brain regions and to other models of autism. Markram aims to eventually build detailed computer models of brains of mammals to pioneer simulation-based research in the neuroscience which could serve to aggregate, integrate, unify and validate our knowledge of the brain and to use such a facility as a new tool to explore the emergence of intelligence and higher cognitive functions in the brain, and explore hypotheses of diseases as well as treatments.

Pierre J. Magistretti is an internationally-recognized neuroscientist who has made significant contributions in the field of brain energy metabolism. His group has discovered some of the cellular and molecular mechanisms that underlie the coupling between neuronal activity and energy consumption by the brain. This work has considerable ramifications for the understanding of the origin of the signals detected with the current functional brain imaging techniques used in neurological and psychiatric research (see for example Magistretti et al, Science, 283: 496 – 497, 1999). He is the author of over 100 articles published in peer-reviewed journals. He has given over 80 invited lectures at international meetings or at universities in Europe and North America, including the 2000 Talairach Lecture at the “Functional Mapping of the Human Brain Conference”. In November 2000 he has been a “Mc Donnel Visiting Scholar” at Washington University School of Medicine. Pierre J. Magistretti is the President-Elect (2002 – 2004) of the Federation of European Neuroscience Societies (FENS) which has a membership of over 15000 European neuroscientists. He has been first president of the Swiss Society for Neuroscience (1997-1999) and the first Chairman of the Department of Neurosciences of the University of Lausanne (1996 – 1998). Pierre J. Magistretti is Professor of Physiology (since 1988) at the University of Lausanne Medical School. He has been Vice-Dean of the University of Lausanne Medical School from 1996 to 2000. Pierre Magistretti, is Director of the Brain Mind Institute at EPFL and Director of the Center for Psychiatric Neuroscience of the University of Lausanne and CHUV. He is also Director of the NCCR SYNAPSY "the synaptic bases of mental diseases". POSITIONS AND HONORS MAIN POSITION HELD • 1988-2004 Professor of Physiology, University of Lausanne Medical School • 1996-2000 Vice-Dean for Preclinical Departments, University of Lausanne Medical School • 2001-2004 Chairman, Department of Physiology, University of Lausanne Medical School • 2004-present Professor and Director, Center for Psychiatric Neuroscience, Department of Psychiatry, University of Lausanne Medical School and Hospitals (UNIL-CHUV) (Joint appointment with EPFL) • 2005-2008 Professor and Co-Director, Brain Mind Institute, Federal Institute of Technology (EPFL), Lausanne (Joint appointment with UNIL-CHUV) • 2007-present Chairman of the Scientific Advisory Board of Centre d’Imagerie Biomédicale (CIBM), an Imaging Consortium of the Universities, University Hospitals of Lausanne and Geneva and of Ecole Polytechnique Fédérale de Lausanne • 2008-present Professor and Director, Brain Mind Institute, Federal Institute of Technology (EPFL), Lausanne Joint appointment with UNIL-CHUV) • 2010-present Director, National Center for Competence in Research (NCCR) “The synaptic bases of mental diseases” of the Swiss National Science Foundation • 2010-present Secretary General, International Brain Research Organization (IBRO) MAIN HONORS AND AWARDS • 1997 Recipient of the Theodore-Ott Prize of the Swiss Academy of Medical Sciences • 2001 Elected Member of Academia Europaea • 2001 Elected Member of the Swiss Academy of Medical Sciences, ad personam • 2002 Recipient of the Emil Kraepelin Guest Professorship, Max Planck Institute für Psychiatry, Münich • 2006 Elected Professor at Collège de France, Paris, International Chair 2007-2008 • 2009 Goethe Award for Psychoanalytic Scholarship, Canadian Psychological Association • 2011 Camillo Golgi Medal Award, Golgi Fondation • 2011 Elected Member of the American College of NeuroPsychopharmacology (ACNP)

ACADEMIC POSITION: Professor, Director of the Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. EDUCATION: • BS MS Salamanca, Spain, 1984 • PhD Cajal Institute, CSIC, and University Autonoma of Madrid, Spain, 1988 PROFESSIONAL EXPERIENCE: • Postdoc at INSERM, Bordeaux, France, and Cajal Institute Madrid, Spain, 1989-1990 • Postdoc at the Open University, UK, 1991-1992, 1996 • Research Associate, Cajal Institute, CSIC, Madrid, 1993-1995 • Associate Professor Tenured, UNED University, Madrid, 1996-2003 • Sabbatical Professor, University of Bern, Switzerland, 2002-2003 • Assistant Professor Tenure-Track, EPFL, 2003-2007 • Associate Professor Tenured, EPFL, 2007-2012 • Full Professor, EPFL, 2012- • Director, Brain Mind Institute, EPFL, 2012- PRINCIPAL BOARDS: • President, European Brain and Behavior Society (EBBS), 2009-2012 • Editor-in-Chief “Frontiers in Behavioral Neuroscience” • Member of Scientific Advisory Panel, European College Neuropsychopharmacology (ECNP) • Member of the European Dana Alliance for the Brain (EDAB) • Associate Editor “Frontiers in Neuroscience” • Editorial Board Member “Neurobiology of Learning and Memory” • Editorial Board Member “Journal of Psychiatry Research” • Editorial Board Member “Stress” • Editorial Board Member “Biology of Mood and Anxiety Disorders” • Editorial Board Member “Neuroscience and Biobehavioral Reviews”