Developmental Brain Physiology and Pathology
Team Leader : Laurent GROC
Laurent GROC is Exceptional Class Research Director (DRCE CNRS) at the CNRS and Université de Bordeaux, head of the Team Developmental Brain Physiology and Pathology, and deputy director of the Interdisciplinary Institute for Neuroscience. His research focuses on the cellular and molecular mechanisms underlying the maturation of glutamate synapses in physiology and neuropsychiatric conditions, such as psychosis. He received his Ph.D. in Neurosciences in 2000 from Wayne State University (Michigan, USA) and Université de Lyon (France). He then joined the Department of Physiology at the University of Goteborg (Sweden) as a postdoctoral fellow to investigate the physiology of developing synapses. In 2004, he was appointed CNRS young investigator (CR) in Bordeaux to decrypt how excitatory synapses mature using an original combination of approaches. He received several prestigious awards, including the 2008 CNRS Young Investigator Award, 2009 Young Investigator Biology Award of the French Science Academy, 2015 Prix Foulon of the French Science Academy, 2015 Prix Dassault, 2016 Human Frontier Science Program Award, 2020 ERC Synergy Award, and 2022 CNRS Silver Medal. In 2020, he has been nominated Guest Professor at the Sahlgrenska Academy in Sweden. Biosketch.
Our aim is to uncover the cellular and molecular mechanisms underlying the maturation of glutamatergic synapses and brain cell networks in a physiological condition as well as in models of neuropsychiatric disorders, such as psychosis. We focus our attention on the interplay between neurotransmitter (glutamatergic, GABAergic and monoaminergic) and immune systems.As an example, we dissect how autoantibodies directed against neurotransmitter receptors and purified from patients with neuropsychiatric symptoms alter synaptic, network and behavioural functions. Finally, we explore how the extracellular space (ECS) of the brain shape cell communication and protein dynamics throughout the nervous system. To tackle these challenges, we develop and use different approaches, such as single molecule imaging in brain tissue, super-resolution imaging, FRET-FLIM, molecular biology, biochemistry, electrophysiology, and behavioural tests.
Autoimmunity in neuropsychiatric disorders: molecular, cellular and behavioural explorationMORE
Glutamate - Dopamine receptor interplay: from physiology to brain disordersMORE
Psychotomimetic drugs: molecular, cellular and behavioural mechanisms of actionMORE
Immunoglobulin dynamics in the brainMORE
Maturation of the NMDA receptor trafficking: molecular and cell type determinants in health and psychiatric diseasesMORE
Immun'Optic Screening PlatformMORE
Retrovirus, inflammation and psychosis: a missing link identified!
Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis
Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral origin alter brain cell communication remain poorly understood. Here, we combined single-molecule tracking, calcium imaging, and behavioral approaches to demonstrate that the envelope protein (Env) of HERV type W, which is normally silenced but expressed in patients with neuropsychiatric conditions, alters the N-methyl-d-aspartate receptor (NMDAR)–mediated synaptic organization and plasticity through glia- and cytokine-dependent changes. Env expression in the developing hippocampus was sufficient to induce behavioral impairments at the adult stage that were prevented by Env neutralization or tuning of NMDAR trafficking. Thus, we show that a HERV gene product alters glutamate synapse maturation and generates behavioral deficits, further supporting the possible etiological interplay between genetic, immune, and synaptic factors in psychosis.
Authors: E.M. Johansson, D. Bouchet, R. Tamouza, P. Ellul, AS. Morr, E. Avignone, R. Germi, M. Leboyer, H. Perron and L. Groc
NMDA receptor along dendrites - PNAS, September 2020
Hippocampal pyramidal neurons are characterized by a unique arborization subdivided in segregated dendritic domains receiving distinct excitatory synaptic inputs with specific properties and plasticity rules that shape their respective contributions to synaptic integration and action potential firing. Although the basal regulation and plastic range of proximal and distal synapses are known to be different, the composition and nanoscale organization of key synaptic proteins at these inputs remains largely elusive. Here we used superresolution imaging and single nanoparticle tracking in rat hippocampal neurons to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDA receptors (NMDARs) -which play key roles in the use-dependent adaptation of glutamatergic synapses- along the dendritic arbor. We report significant changes in the nanoscale organization of GluN2B-NMDARs between proximal and distal dendritic segments, whereas the topography of GluN2A-NMDARs remains similar along the dendritic tree. Remarkably, the nanoscale organization of GluN2B-NMDARs at proximal segments depends on their interaction with calcium/calmodulin-dependent protein kinase II (CaMKII), which is not the case at distal segments. Collectively, our data reveal that the nanoscale organization of NMDARs changes along dendritic segments in a subtype-specific manner and is shaped by the interplay with CaMKII at proximal dendritic segments, shedding light on our understanding of the functional diversity of hippocampal glutamatergic synapses.
Authors: Joana S. Ferreira, Julien P. Dupuis, Blanka Kellermayer, Nathan Bénac, Constance Manso, Delphine Bouchet, Florian Levet, Corey Butler, Jean-Baptiste Sibarita, and Laurent Groc
Laurent Groc, Médaille d'argent du CNRS 2022
The CNRS Silver Medal is awarded to researchers for the originality, quality and importance of their work, recognized at national and international level.
Congratulations to Laurent Groc, CNRS research director and team leader at the IINS, one of the 22 laureates distinguished for this year 2022.
Cf. CNRS website here
NMDA receptor functions in health and disease: Old actor, new dimensions, Neuron - May 23
Julien P. Dupuis, Olivier Nicole, Laurent Groc
The PHRC TiM-DepisT project
The PHRC TiM-DepisT project is a national hospital-based clinical research project. Its aim is to detect (DepisT) and treat (TiM = immunomodulatory therapy) the presence of autoimmunity in people suffering from psychiatric disorders (psychosis).
Led by Frederic Villega (CHU Bordeaux/IINS) and involving 9 University Hospitals across France, the project involves psychiatrists, child psychiatrists, neuropaediatricians and researchers. Psychiatrists Marion Leboyer from the Fondamental Foundation, Bruno Aouizerate, David Misdrahi, Sebastien Gard and Anouck Amestoy from Bordeaux Charles Perrens CHU, will be working hand in hand with researchers from Laurent Groc's IINS team (Delphine Bouchet, Olivier Nicole, Julien Dupuis, Helene Grea) and the Bordeaux CHU immunology department team (Isabelle Pellegrin, Patrick Blanco, Cecile Bordes).
The project was born in 2019 thanks to collaborative work between the research team of Laurent Groc (CNRS/University of Bordeaux), and the neuropaediatrician Frederic Villega, with the support of the Clinical Research Department of Bordeaux University Hospital.
In terms of funding, the project was supported by the the French government with the “Direction Generale de l'Offre de Soins”. The strength of this project lies both in the clinical question and in the fundamental and technological advances made by the IINS research laboratory. IINS researchers have built a diagnostic platform, coordinated by Delphine Bouchet (CNRS Research Engineer). It enables the presence of pathological autoantibodies to be detected with a high degree of reliability, which is a fundamental issue in this field. This effort began more than 10 years ago with the support of the “Fondation de le Recherche Medicale” (FRM), the Fondation “FondaMental”, and more recently, thanks to the award in 2019 of the SPARK prize from the University of Bordeaux. Thanks to the emergence of this innovative platform, the clinical project can now be rolled out with a budget of one million euros.
The project has also had a long road ahead, with submissions to many institutions (“Agence nationale de securité du medicament", ethics committees, etc.) and the covid pandemic. Nevertheless, diagnosis and treatment of the disease will be able to begin in October 2023.
The prospects for the PHRC TiM-DepisT project are therefore significant. Between 2024 and 2027, researchers plan to carry out diagnostic research on 1,000 patients. The aim is to detect and provide access to immunotherapy treatment for several dozens of them. This unprecedented system opens up a host of possibilities for the benefit of medicine, which is in the midst of a revolution as a result of the discovery of the multiple implications of autoimmunity.
Frederic Villega has a few words to say about the PHRC TiM-DepisT project :
"As a clinician at the CHU, who has been working with Laurent Groc and his team for many years, I have structured this bridge between the clinical and the technological. This enables us to transfer elements of major fundamental discoveries for the benefit of healthcare! In this way, I've been able to bring together the strengths of Bordeaux University Hospital and the IINS to build an incredibly ambitious project that will provide answers to major burning questions about the new concept of immuno-psychiatry. [...] Laurent Groc was the researcher who, with his team and his international partners, climbed the first steps of an immense edifice concerning the physiopathology of psychiatric illnesses. This project represents immense hope for all mankind. It is, of course, one of many examples of the importance of research to healthcare and the quality of life of the men and women of tomorrow. [...] The aim of this research project is to answer 2 major questions in the context of mental health care: How prevalent is dysimmunity among the many factors involved in the pathophysiology of the diagnosis of psychosis? And to what extent can these patients, with an autoimmunity, respond to immunomodulatory therapy? This project could prove to be a major global turning point in psychiatric diagnosis and treatment, offering millions of families the hope of a brighter future!
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« Alumni & Guests »
ALUMNI and GUESTS
Former group members
- Lucie BARD (2006-2010) PhD student
- Hongyu ZHANG (2009-2011) Post-doc
- Lenka MIKASOVA (2009-2012) Post-doc
- François GEORGES (2011-2013) CNRS researcher
- Christelle GLANGETAS (2011-2013) PhD student
- Delphine GIRARD (2011-2013) CNRS engineer
- Laurent LADEPECHE (2009-2013) PhD student
- Ciaran MURPHY-ROYAL (2010-2014) PhD student
- Agnès ESPANA (2011-2014) Post-doc
- Aurelia LE DANTEC (2012-2014) CNRS engineer
- Juan VARELA (2011-2015) Post-doc
- Charlotte BERTOT (2013-2016) PhD student
- Julie JEZEQUEL (2011-2017) PhD student
- Pauline DURAND (2014-2017) CNRS engineer
- Laetitia ETCHEPARE (2012-2017) PhD student
- Blanka KELLERMAYER (2014-2017) PhD student
- Silvia CIAPPELLONI (2013-2017) Post-doc
- Sébastien HABE (2016-2017) CNRS engineer
- Marilyn LEPLEUX (2015-2018) CNRS engineer
- Audrey BARRANGER (2017-2019) CNRS engineer
- Ezequiel SARACENO (2017-2019) Post-doc
- Tingting HUANG (2017-2019) PhD student
- Pauline LETARD (2015-2019) PhD student
- Elise GOYET (2017-2019) CNRS engineer
- Emily JOHANSSON (2013-2020) Post-doc
- Elena AVIGNONE (2013-2020) Bordeaux University researcher
- Alexandra FERNANDES (2015-2020) PhD student
- François MAINGRET (2013-2021) CNRS researcher
- Joana FERREIRA (2013-2021) Post-Doc
- Diego GRASSI (2018-2021) Post-Doc
- Elodie COUGOUILLES (2020) UB engineer
- Constance MANSO (2018-2021) CNRS/UB engineer
- Mar PETIT-PEDROL (2020-2022) Post-Doc
- Laurine BASTARDO (2020-2023) CNRS engineer
- Theo BAURBERG (2020-2023) CNRS engineer
- Daniel HUNTER (2019-2023) PhD Student
- Inma GONZALEZ (2011-2012) Pamplona University
- Amber KERKHOFS (2012) Utrecht University
- Yuki MIURA (2013-2014) Tsukuka University
- Pr. Marion LEBOYER (2016) Hopital Mondor, Fondation FondaMental
- Kevin JEHASSE (2019) Liège University
- Nila VAN OVERBEEK (2019-2020) Amsterdam University
- Pin Wu LIU (2020) Kyoto University Graduate School of Medicine
- Alessandro CHIOINO (2022) Lausanne University
- Vanesa SALAZAR SANCHEZ (2022), Edimbourg University
- Catarina RODRIGUES (2022-2023) ERASMUS - Coimbra University
- Estibaliz MAUDES (2023) Barcelona University
- Andres BARRIA (2023) Professor of Physiology & Biophysics, University of Washington