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Developmental Brain Physiology and Pathology

Team Leader : Laurent GROC

Laurent GROC is Research Director (DR1 CNRS) at the CNRS and Université de Bordeaux, head of the team Development, 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, and 2016 Human Frontier Science Program Award. In 2020, he has been nominated Guest Professor at the Sahlgrenska Academy in Sweden. Biosketch.

General objective

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. 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.

Research Projects

Autoimmunity in neuropsychiatric disorders: molecular, cellular and behavioural exploration

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Glutamate - Dopamine receptor interplay: from physiology to brain disorders

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Psychotomimetic drugs: molecular, cellular and behavioural mechanisms of action

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Immunoglobulin dynamics in the brain

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Maturation of the NMDA receptor trafficking: molecular and cell type determinants in health and psychiatric diseases

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Immun'Optic Screening Platform

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Expertise

  • Single nanoparticle tracking
  • Electrophysiology
  • Biochemistry and protein engineering
  • Super-resolution microscopy
  • News

    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

    - Science Advances 17 Jul 2020: Vol. 6, no. 29, eabc0708 - DOI: 10.1126/sciadv.abc0708
    - Contacts: Emily M. Johannson and Laurent Groc
    + More details on the Neurocampus website here

    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

    Selected Publications

  • Ferreira JS, Dupuis JP, Kellermayer B, Bénac N, Manso C, Bouchet D, Levet F, Butler C, Sibarita JB, Groc L.
  • Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites PNAS (2020)
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  • Johansson EM, Bouchet D, Tamouza R, Ellul P, Morr AS, Avignone E, Germi R, Leboyer M, Perron H, Groc L
  • Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis Science Adv. (2020)
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  • Groc L, Choquet D
  • Linking glutamate receptor movements and synapse function Science (2020)
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  • Ciappelloni S, Bouchet D, Dubourdieu N, Boué-Grabot E, Kellermayer B, Manso C, Marignier R, Oliet SHR, Tourdias T, Groc L
  • Aquaporin-4 Surface Trafficking Regulates Astrocytic Process Motility and Synaptic Activity in Health and Autoimmune Disease Cell Reports (2019)
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  • Kellermayer B, Ferreira JS, Dupuis J, Levet F, Grillo-Bosch D, Bard L, Linarès-Loyez J, Bouchet D, Choquet D, Rusakov DA, Bon P, Sibarita JB, Cognet L, Sainlos M, Carvalho AL, Groc L
  • Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses Neuron (2018)
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  • Jézéquel J, Johansson EM, Leboyer M, Groc L
  • Pathogenicity of Antibodies against NMDA Receptor: Molecular Insights into Autoimmune Psychosis Trends Neurosci. (2018)
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  • Jézéquel J, Johansson EM, Dupuis JP, Rogemond V, Gréa H, Kellermayer B, Hamdani N, Le Guen E, Rabu C, Lepleux M, Spatola M, Mathias E, Bouchet D, Ramsey AJ, Yolken RH, Tamouza R, Dalmau J, Honnorat J, Leboyer M, Groc L
  • Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients Nature Commun. (2017)
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  • Ferreira JS, Papouin T, Ladépêche L, Yao A, Langlais VC, Bouchet D, Dulong J, Mothet JP, Sacchi S, Pollegioni L, Paoletti P, Oliet SHR, Groc L
  • Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses eLife (2017)
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  • Godin AG, Varela JA, Gao Z, Danné N, Dupuis JP, Lounis B, Groc L*, Cognet L*
  • Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain Nature Nanotechnol. (2017)
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  • Varela JA, Dupuis JP, Etchepare L, Espana A, Cognet L, Groc L
  • Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices Nature Commun. (2016)
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  • Murphy-Royal C, Dupuis JP, Varela JA, Panatier A, Pinson B, Baufreton J, Groc L*, Oliet SH*
  • Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission Nature Neurosci. (2015)
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  • Ladepeche L, Dupuis JP, Bouchet D, Doudnikoff E, Yang L, Campagne Y, Bézard E, Hosy E, Groc L
  • Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses EMBO J. (2014)
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  • Ladepeche L, Dupuis JP, Bouchet D, Doudnikoff E, Yang L, Campagne Y, Bézard E, Hosy E, Groc L
  • Single-molecule imaging of the functional crosstalk between surface NMDA and dopamine D1 receptors PNAS (2013)
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  • Zhang H, Etherington LA, Hafner AS, Belelli D, Coussen F, Delagrange P, Chaouloff F, Spedding M, Lambert JJ, Choquet D, Groc L
  • Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule Molecular Psychiatry (2013)
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  • Mikasova L, De Rossi P, Bouchet D, Georges F, Rogemond V, Didelot A, Meissirel C, Honnorat J, Groc L
  • Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis Brain (2012)
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  • Bard L, Sainlos M, Bouchet D, Cousins S, Mikasova L, Breillat C, Stephenson FA, Imperiali B, Choquet D, Groc L
  • Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins PNAS (2010)
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  • Krugers HJ, Hoogenraad CC, Groc L
  • The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation Nature Review Neurosci. (2010)
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  • Groc L, Choquet D, Chaouloff F
  • The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation Nature Neurosci. (2008)
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  • Groc L, Heine M, Cousins SL, Stephenson FA, Lounis B, Cognet L, Choquet D
  • NMDA receptor surface mobility depends on NR2A-2B subunits PNAS (2006)
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  • Groc L, Gustafsson B, Hanse E
  • AMPA signalling in nascent glutamatergic synapses: there and not there! Trends Neurosci. (2006)
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  • Groc L, Heine M, Cognet L, Brickley K, Stephenson FA, Lounis B, Choquet D
  • Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors Nature Neurosci. (2004)
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    Members

    « Researcher »

    DUPUIS Julien Researcher julien.dupuis@u-bordeaux.fr +33533514762
    GREA Helene Researcher helene.grea@u-bordeaux.fr +33533514762
    GROC Laurent Researcher laurent.groc@u-bordeaux.fr +33533514702
    MAINGRET Francois Researcher francois.maingret@u-bordeaux.fr +33533514762

    « Technical Staff »

    BENAC Nathan Technical staff nathan.benac@u-bordeaux.fr +33533514781
    BOUCHET TESSIER Delphine Technical staff delphine.bouchet@u-bordeaux.fr +33533514762
    COUGOUILLES Elodie Technical staff elodie.cougouilles@u-bordeaux.fr +33533514781
    MANSO Constance Technical staff constance.manso@u-bordeaux.fr +33533514781
    ROUDEAU Stéphane Technical staff roudeau@cenbg.in2p3.fr +33533514762

    « Postdoc »

    GRASSI Diego Postdoc diego.grassi@u-bordeaux.fr +33533514781
    PETIT PEDROL Mar Postdoc mar.petit@u-bordeaux.fr +33533514761

    « PhD student »

    FERNANDES Alexandra PhD student alexandra.fernandes@u-bordeaux.fr +33533514781
    HUNTER Daniel PhD student daniel.hunter@u-bordeaux.fr +33533514761
    JAMET Zoé PhD student zoe.jamet@u-bordeaux.fr +33533514761
    Villega Frédéric PhD student frederic.villega@u-bordeaux.fr +33533514762

    « Student »

    BAURBERG Théo Student theo.baurberg@u-bordeaux.fr +33533514781