Pierre Magistretti | EPFL Graph Search

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 dImagerie 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)

Lactate supply overtakes glucose when neural computational and cognitive loads scale up

Pierre Magistretti

Neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks, and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting longterm synaptic plasticity evoked by high-stimulation load activity patterns and high attentional load in cognitive tasks and glucose being sufficient for less demanding neural computation and learning tasks. Indeed, we show that lactate is mandatory for demanding neural computation, such as theta-burst stimulation, while glucose is sufficient for lighter forms of activity-dependent long-term potentiation (LTP), such as spike timing-dependent plasticity (STDP). We find that subtle variations of spike number or frequency in STDP are sufficient to shift the on-demand fueling from glucose to lactate. Finally, we demonstrate that lactate is necessary for a cognitive task requiring high attentional load, such as the object-in-place task, and for the corresponding in vivo hippocampal LTP expression but is not needed for a less demanding task, such as a simple novel object recognition. Overall, these results demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.

NATL ACAD SCIENCES2022

The critical periods of cerebral plasticity: A key aspect in a dialog between psychoanalysis and neuroscience centered on the psychopathology of schizophrenia

Pierre Magistretti

Through research into the molecular and cellular mechanisms that occur during critical periods, recent experimental neurobiological data have brought to light the importance of early childhood. These have demonstrated that childhood and early environmental stimuli play a part not only in our subjective construction, but also in brain development; thus, confirming Freud's intuition regarding the central role of childhood and early experiences of the environment in our psychological development and our subjective outcomes. "Critical periods" of cerebral development represent temporal windows that mark favorable, but also circumscribed, moments in developmental cerebral plasticity. They also vary between different cortical areas. There are, therefore, strictly defined temporal periods for learning language, music, etc., after which this learning becomes more difficult, or even impossible, to acquire. Now, research into these critical periods can be seen as having a significant part to play in the interdisciplinary dialog between psychoanalysis and neurosciences with regard to the role of early experiences in the etiology of some psychopathological conditions. Research into the cellular and molecular mechanisms controlling the onset and end of these critical periods, notably controlled by the maturation of parvalbumin-expressing basket cells, have brought to light the presence of anomalies in the maturation of these neurons in patients with schizophrenia. Starting from these findings we propose revisiting the psychoanalytic theories on the etiology of psychosis from an interdisciplinary perspective. Our study works from the observation, common to both psychoanalysis and neurosciences, that experience leaves a trace; be it a "psychic" or a "synaptic" trace. Thus, we develop a hypothesis for an "absence of trace" in psychosis; reexamining psychosis through the prism of the biological theory of critical periods in plasticity.

FRONTIERS MEDIA SA2022

Excitation states of metabolic networks predict dose-response fingerprinting and ligand pulse phase signalling

Jay Coggan, Daniel Keller, Pierre Magistretti, Henry Markram, Felix Schürmann

With a computational model of energy metabolism in an astrocyte, we show how a system of enzymes in a cascade can act as a functional unit of interdependent reactions, rather than merely a series of independent reactions. These systems may exist in multiple states, depending on the level of stimulation, and the effects of substrates at any point will depend on those states. Response trajectories of metabolites downstream from cAMP-stimulated glycogenolysis exhibit a host of non-linear dynamical response characteristics including hysteresis and response envelopes. Dose-dependent phase transitions predict a novel intracellular signalling mechanism and suggest a theoretical framework that could be relevant to single cell information processing, drug discovery or synthetic biology. Ligands may produce unique dose-response fingerprints depending on the state of the system, allowing selective output tuning. We conclude with the observation that state- and dose-dependent phase transitions, what we dub "ligand pulses" (LPs), may carry information and resemble action potentials (APs) generated from excitatory postsynaptic potentials. In our model, the relevant information from a cAMP-dependent glycolytic cascade in astrocytes could reflect the level of neuromodulatory input that signals an energy demand threshold. We propose that both APs and LPs represent specialized cases of molecular phase signalling with a common evolutionary root. (C) 2019 The Authors. Published by Elsevier Ltd.

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2020

The critical periods of cerebral plasticity: A key aspect in a dialog between psychoanalysis and neuroscience centered on the psychopathology of schizophrenia

Pierre Magistretti

FRONTIERS MEDIA SA2022