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Dynamic organization & Function of synapses

"Progress in science depends on new techniques, new discoveries and new ideas, probably in that order." Sydney Brenner

Team Leader: Daniel Choquet

Contact: Daniel CHOQUET

Tel. (+33)5 33 51 47 15


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Daniel Choquet obtained an engineering degree from Ecole Centrale (Paris, France) in 1984. He then got attracted to neuroscience and completed his PhD in the lab of Henri Korn at the Pasteur Institute (Paris), studying ion channels in lymphocytes. He got appointed tenure Research officer at the CNRS in 1988. He then performed a post-doctoral/sabbatical at the Duke University (North Carolina, USA) in the laboratory of Michael Sheetz where he studied the regulation of integrin-cytoskeletal linkage by force, and demonstrated that cells can sense and respond to extracellular traction. He then setup his group in Bordeaux (France) at the Institute for Neuroscience where he got a directorship position at the CNRS. He launched an interdisciplinary program on the combination of physiology, cell and chemical biology and high resolution imaging to study the functional role of the dynamic organization and trafficking of neurotransmitter receptors in synaptic transmission. He is now heading the Institute for Interdisciplinary Neuroscience and the Bordeaux Imaging Center core facility. He is also the director of the center of excellence BRAIN, Bordeaux Region Aquitaine Initiative for Neuroscience.

He has been the recipient of several awards including the 1990 Bronze Medal from the CNRS, the Research prize from the Fondation pour la Recherche Médicale (FRM), 1997, the Grand Prix from the French Academy of Sciences, Prix du CEA and the 2009 Silver Medal from the CNRS. He is a Member of the Institut de France, the French Science Academy since November 2010 and Officier de la Légion d’honneur. He has been awarded three ERC advanced grants in 2008, 2013 and 2018.

The team develops several research topics, combining neuroscience, physics and chemistry in order to unravel the dynamics and nanoscale organization of multimolecular receptor complexes and their functional rôle in glutamatergic synaptic transmission. Recently, the team has engaged in a major program to analyse and understand the interplay between AMPA type glutamate receptor nanoscale dynamics, synaptic plasticity and memory formation in the healthy and diseased brain.

Project Summary

We have a transdisciplinary approach to study the interplay between the organizational dynamics of the molecular components of glutamatergic synapses and synaptic transmission. Our projects build on our recent findings that:
  • trafficking of neuronal molecules such as glutamate receptors is highly dynamic,
  • regulations of protein-protein interactions play key roles in the control of this trafficking at different steps, including lateral diffusion, endo and exocytosis,
  • modulation of glutamate receptor trafficking has a profound impact on synaptic transmission, including on both short and long term post-synaptic plasticity.

  • By combining the expertise of chemists, biochemists, cell biologists, biophysicists and neurophysiologists, we will develop 3 main research axes:
  • dynamics and physical-chemistry of the macro-molecular complexes of the synapse,
  • nano-scale organization and dynamics of synaptic proteins and membrane trafficking,
  • impact of the dynamic of synapse organization on synaptic physiology.

  • Results obtained in these three axes will be constantly integrated to provide a global view of glutamatergic synapse physiology, from nano-scale interactions to function up to higher brain functions such as memory formation and retrieval.

    Anna Brachet

    Cytoskeleton and membrane interplay in synaptic organization and transmission.


    Françoise Coussen

    Impact of auxiliary proteins on AMPAR transport, trafficking and physiology.


    Eric Hosy

    Impact of AMPAR dynamic nano-organization on synaptic transmission.


    David Perrais

    Nano-scale organization, dynamics of synaptic proteins and membrane trafficking.

    Matthieu Sainlos

    Exploiting techniques from chemistry, biophysics and protein engineering to develop novel tools and approaches to elucidate biological processes involved in the basis of synaptic transmission.

    Group picture


    Alumni and Guests

    Check here where are, now, former group members.

    Recent Publications

    The next generation of approaches to investigate the link between synaptic plasticity and learning.
    Humeau, Y. and Choquet, D. Nature Neuroscience. 2019 22, 1536-1543.

    A super-resolution platform for correlative live single-molecule imaging and STED microscopy.
    Inavalli, V., Lenz, M.O., Butler, C., Angibaud, J., Compans, B., Levet, F., Tonnesen, J., Rossier, O., Giannone, G., Thoumine, O., et al. Nature Methods. 2019 doi: 10.1038/s41592-019-0611-8.

    Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.
    Rimbault, C., Maruthi, K., Breillat, C., Genuer, C., Crespillo, S., Puente-Munoz, V., Chamma, I., Gauthereau, I., Antoine, S., Thibaut, C., et al. Nature Communication. 2019 10, 4521.

    Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis.
    Rosendale, M., Van, T.N.N., Grillo-Bosch, D., Sposini, S., Claverie, L., Gauthereau, I., Claverol, S., Choquet, D., Sainlos, M., and Perrais, D. Nature Communication. 2019 10, 4462.

    Linking Nanoscale Dynamics of AMPA Receptor Organization to Plasticity of Excitatory Synapses and Learning.
    Choquet, D. J. Neuroscience. 2018 38, 9318-9329.

    Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency.
    Haas, K.T., Compans, B., Letellier, M., Bartol, T.M., Grillo-Bosch, D., Sejnowski, T.J., Sainlos, M., Choquet, D., Thoumine, O., and Hosy, E. Elife. 2018 7

    Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models.
    Zhang, H., Zhang, C., Vincent, J., Zala, D., Benstaali, C., Sainlos, M., Grillo-Bosch, D., Daburon, S., Coussen, F., Cho, Y., David DJ, Saudou, F, Humeau, Y. and Choquet, D., Thoumine, O., and Hosy, E. Nature Communications. 2018 7

    CaMKII Metaplasticity Drives A beta Oligomer-Mediated Synaptotoxicity.
    Opazo, P., da Silva, S.V., Carta, M., Breillat, C., Coultrap, S.J., Grillo-Bosch, D., Sainlos, M., Coussen, F., Bayer, K.U., Mulle, C., and Choquet, D. Cell Report. 2018 23, 3137-3145.

    Neuronal Activity and Intracellular Calcium Levels Regulate Intracellular Transport of Newly Synthesized AMPAR.
    Hangen, E., Cordelieres, F.P., Petersen, J.D., Choquet, D., and Coussen, F. Cell Report. 2018 24, 1001.

    Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses.
    Kellermayer, B., Ferreira, J.S., Dupuis, J., Levet, F., Grillo-Bosch, D., Bard, L., Linares-Loyez, J., Bouchet, D., Choquet, D., Rusakov, D.A., et al. (2018). Neuron 100, 106-119 e107.

    Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors.
    Penn AC, Zhang CL, Georges F, Royer L, Breillat C, Hosy E, Petersen JD, Humeau Y, Choquet D. Nature. 2017 Sept 13

    Localization-based super-resolution imaging meets high-content screening.
    Beghin, A, Kechkar, A, Butler, C, Levet, F, Cabillic, M, Rossier, O, Giannone, G, Galland, R, Choquet, D, and Sibarita, J.B. Nature Methods. 2017 14 1184-1190

    Spatial and Temporal Regulation of Receptor Endocytosis in Neuronal Dendrites Revealed by Imaging of Single Vesicle Formation.
    Rosendale, M, Jullie, D, Choquet, D, and Perrais, D Cell Report. 2017 18, 1840-1847

    Semisynthetic fluorescent pH sensors for imaging exocytosis and endocytosis.
    Martineau, M, Somasundaram, A, Grimm, JB, Gruber, TD, Choquet, D, Taraska, JW, Lavis, LD, and Perrais, D Nature Communication. 2017 8 1412

    Mapping the dynamics and nanoscale organization of synaptic adhesion proteins using monomeric streptavidin.
    Chamma I, Letellier M, Butler C, Tessier B, Lim KH, Gauthereau I, Choquet D, Sibarita JB, Park S, Sainlos M, Thoumine O. Nat Commun. 2016 Mar 16

    Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity.
    Klaassen RV, Stroeder J, Coussen F, Hafner AS, Petersen JD, Renancio C, Schmitz LJ, Normand E, Lodder JC, Rotaru DC, Rao-Ruiz P, Spijker S, Mansvelder HD, Choquet D, Smit AB. Nat Commun. 2016 Mar (Klaassen RV, Stroeder J, Coussen F, co first-authors; Choquet D, Smit AB, co last-authors)

    Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95..
    Hafner AS, Penn AC, Grillo-Bosch D, Retailleau N, Poujol C, Philippat A, Coussen F, Sainlos M, Opazo P, Choquet D. Neuron. 2015 Apr

    Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin.
    Constals A, Penn AC, Compans B, Toulmé E, Phillipat A, Marais S, Retailleau N, Hafner AS,Coussen F, Hosy E, Choquet D. Neuron. 2015 Feb

    Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95
    Nair D, Hosy E, Petersen JD, Constals A, Giannone G, Choquet D, Sibarita JB. J Neurosci. 2013 Aug 7 (Nair D, Hosy E, co first-authors; Choquet D, Sibarita JB, co last-authors)

    Caged mono- and divalent ligands for light-assisted disruption of PDZ domain-mediated interactions
    Sainlos M, Iskenderian-Epps WS, Olivier NB, Choquet D, Imperiali B. J Am Chem Soc. 2013 Mar 27

    Neurexin-1b Binding to Neuroligin-1 Triggers the Preferential Recruitment of PSD-95 versus Gephyrin through Tyrosine Phosphorylation of Neuroligin-1.
    Giannone G, Mondin M, Grillo-Bosch D, Tessier B, Saint-Michel E, Czöndör K, Sainlos M, Choquet D, Thoumine O. Cell Rep. 2013 Jun 27