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

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
 

Selected Publications

Mar Petit-Pedrol, Laurent Groc

Regulation of membrane NMDA receptors by dynamics and protein interactions J. Cell Biol. (2021)
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Etchepare L, Gréa H, Durand P, Bouchet D, Groc L

NMDA receptor membrane dynamics tunes the firing pattern of midbrain dopaminergic neurons J. Physiol (2021)
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Hosokawa T, Liu PW, Cai Q, Ferreira JS, Levet F, Butler C, Sibarita JB, Choquet D, Groc L, Hosy E, Zhang M, Hayashi Y

CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation Nature Neurosci. (2021)
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Wollmuth LP, Chan K, Groc L

The diverse and complex modes of action of anti-NMDA receptor autoantibodies Neuropharmacol. (2021)
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Espana A, Seth H, Jézéquel J, Huang T, Bouchet D, Lepleux M, Gréa H, Bechter K, Schneider M, Hanse E, Groc L

Alteration of NMDA receptor trafficking as a cellular hallmark of psychosis Translational Psychiatry (2021)
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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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« 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

Guests

• 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