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Dynamic Organization of Synapses and Function

Team Leader : Daniel Choquet

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

Daniel Choquet is a research director at the CNRS. He obtained an engineering degree from Ecole Centrale (Paris, France) in 1984 and completed his PhD in the lab of Henri Korn at the Pasteur Institute (Paris), studying ion channels in lymphocytes. He did a post-doctoral/sabbatical at Duke University (North Carolina, USA) in the laboratory of Michael Sheetz where he studied the regulation of integrin-cytoskeletal linkage by force. He setup his group in Bordeaux (France) at the Institute for Neuroscience and 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. He is a Member of the French Science Academy and has been awarded three consecutive ERC advanced grants. BioSketch (PDF). Personal page.

General objective

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 leaders (Click to reach subprojects)

Anna Brachet Daniel Choquet Françoise Coussen Eric Hosy Matthieu Sainlos

Research Projects

Team Project Summary

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Cytoskeleton and membrane interplay in synaptic organization and transmission (Anna Brachet).

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Chemical Biology and Protein Engineering (Matthieu Sainlos)

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Impact of auxiliary proteins on AMPAR transport, trafficking and physiology (Françoise Coussen).

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Impact of AMPAR dynamic nano-organization on synaptic transmission (Eric Hosy).

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Contribution of AMPAR surface trafficking to Short and long term synaptic plasticity (Daniel Choquet)

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Expertise

  • Super Resolution Microscopy
  • Slice physiology
  • Chemical biology, Protein Engineering
  • Biochemistry
  • News

    Co-organization and coactivation of AMPAR, NMDAR, and mGluR

    Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses.

    The nanoscale co-organization of neurotransmitter receptors facing presynaptic release sites is a fundamental determinant of their coactivation and of synaptic physiology. At excitatory synapses, how endogenous AMPARs, NMDARs, and mGluRs are co-organized inside the synapse and their respective activation during glutamate release are still unclear. Combining single-molecule super resolution microscopy, electrophysiology, and modeling, we determined the average quantity of each glutamate receptor type, their nanoscale organization, and their respective activation. We observed that NMDARs form a unique cluster mainly at the center of the PSD, while AMPARs segregate in clusters surrounding the NMDARs.mGluR5 presents a different organization and is homogenously dispersed at the synaptic surface. From these results, we build a model predicting the synaptic transmission properties of a unitary synapse, allowing better understanding of synaptic physiology.

    Authors: Julia Goncalves, Tomas M. Bartol, Côme Camus, Florian Levet, Ana Paula Menegolla,Terrence J. Sejnowski, Jean-Baptiste Sibarita, Michel Vivaudou, Daniel Choquet and Eric Hosy

    - Publication in PNAS, June 8, 2020 https://doi.org/10.1073/pnas.1922563117
    - Contact: Eric Hosy

    + Cf Bordeaux Neurocampus website here

    AMPA receptor nanoscale dynamic organization and synaptic plasticities

    Review on “AMPA receptor nanoscale dynamic organization and synaptic plasticities” in Current Opinion in Neurobiology 2020

    The emergence of new imaging techniques and molecular tools has refreshed our understanding of the principles of synaptic transmission and plasticity. Superresolution imaging and biosensors for measuring enzymatic activities in live neurons or neurotransmitter levels in the synaptic cleft are giving us an unprecedented integrated and nanoscale view on synaptic function. Excitatory synapses are now conceptualized as organized in subdomains, enriched with specific scaffolding proteins and glutamate receptors, molecularly organized with respect to the pre-synaptic source of glutamate.

    This new vision of basic synaptic transmission changes our understanding of the molecular modifications which sustain synaptic plasticities. Long-term potentiation can no longer be explained simply by an increase in receptor content at the synapse. We review here the latest data on the role of nanoscale and dynamic organization of AMPA type glutamate receptors on synaptic transmission at both basal state and during short and long-term plasticities.

    - Current Opinion in Neurobiology - Volume 63, August 2020, Pages 137-145 https://doi.org/10.1016/j.conb.2020.04.003
    - Contacts: Daniel Choquet and Eric Hosy

    A discrete presynaptic vesicle cycle for neuromodulator receptors - Neuron, December 2019

    A major function of GPCRs is to inhibit presynaptic neurotransmitter release, requiring ligand-activated receptors to couple locally to effectors at terminals. The current understanding of how this is achieved is through receptor immobilization on the terminal surface. Here, we show that opioid peptide receptors, GPCRs that mediate highly sensitive presynaptic inhibition, are instead dynamic in axons. Opioid receptors diffuse rapidly throughout the axon surface and internalize after ligand-induced activation specifically at presynaptic terminals. We delineate a parallel regulated endocytic cycle for GPCRs operating at the presynapse, separately from the synaptic vesicle cycle, which clears activated receptors from the surface of terminals and locally reinserts them to maintain the diffusible surface pool. We propose an alternate strategy for achieving local control of presynaptic effectors that, opposite to using receptor immobilization and enforced proximity, is based on lateral mobility of receptors and leverages the inherent allostery of GPCR-effector coupling.

    Damien Jullié, Miriam Stoeber, Jean-Baptiste Sibarita, Hanna L. Zieger, Thomas M. Bartol, Seksiri Arttamangkul, Terrence J. Sejnowski, Eric Hosy, and Mark von Zastrow

    - Neuron. 2019 Dec 5 - doi: 10.1016/j.neuron.2019.11.016.
    - Contact: Eric Hosy

    Multicolor Spectrin labeling (ML Jobin)

    This is a rat hippocampal neuron in culture stained with a series of markers

     

     

    Selected Publications

  • Laurent Groc & Daniel Choquet
  • Linking glutamate receptor movements and synapse function Science (2020)
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  • Julia Goncalves, Tomas M Bartol, Côme Camus, Florian Levet, Ana Paula Menegolla, Terrence J Sejnowski, Jean-Baptiste Sibarita, Michel Vivaudou, Daniel Choquet, Eric Hosy
  • Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses Proc Natl Acad Sci U S A (2020)
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  • Tiago Campelo, Elisabete Augusto, Nicolas Chenouard, Aron de Miranda, Vladimir Kouskoff, Come Camus, Daniel Choquet, Frédéric Gambino
  • AMPAR-Dependent Synaptic Plasticity Initiates Cortical Remapping and Adaptive Behaviors during Sensory Experience Cell Report (2020)
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  • Humeau, Y. and Choquet, D.
  • The next generation of approaches to investigate the link between synaptic plasticity and learning. Nature Neuroscience (2019)
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  • Charlotte Rimbault, Kashyap Maruthi, Christelle Breillat, Camille Genuer, Sara Crespillo, Virginia Puente-Muñoz, Ingrid Chamma, Isabel Gauthereau, Ségolène Antoine, Coraline Thibaut, Fabienne Wong Jun Tai, Benjamin Dartigues, Dolors Grillo-Bosch, Stéphane Claverol, Christel Poujol, Daniel Choquet, Cameron D Mackereth, Matthieu Sainlos
  • Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules Nature Communication (2019)
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  • Emilie Hangen, Fabrice P Cordelières, Jennifer D Petersen, Daniel Choquet, Françoise Coussen
  • Neuronal Activity and Intracellular Calcium Levels Regulate Intracellular Transport of Newly Synthesized AMPAR Cell Report (2018)
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  • Penn, A.C., Zhang, C.L., Georges, F., Royer, L., Breillat, C., Hosy, E., Petersen, J.D., Humeau, Y., and Choquet, D.
  • Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors Nature (2017)
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  • Audrey Constals, Andrew C Penn, Benjamin Compans, Estelle Toulmé, Amandine Phillipat, Sébastien Marais, Natacha Retailleau, Anne-Sophie Hafner, Françoise Coussen, Eric Hosy, Daniel Choquet
  • Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin Neuron (2015)
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  • Anne-Sophie Hafner, Andrew C Penn, Dolors Grillo-Bosch, Natacha Retailleau, Christel Poujol, Amandine Philippat, Françoise Coussen, Matthieu Sainlos, Patricio Opazo, Daniel Choquet
  • Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95 Neuron (2015)
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  • Deepak Nair, Eric Hosy, Jennifer D Petersen, Audrey Constals, Gregory Giannone, Daniel Choquet, Jean-Baptiste Sibarita
  • Super-resolution imaging reveals that AMPA receptors inside synapses are dynamically organized in nanodomains regulated by PSD95 Journal of Neuroscience (2013)
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  • Heine, M., Groc, L., Frischknecht, R., Beique, J.C., Lounis, B., Rumbaugh, G., Huganir, R.L., Cognet, L., and Choquet, D.
  • Surface mobility of postsynaptic AMPARs tunes synaptic transmission Science (2008)
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  • Aren J Borgdorff and Daniel Choquet
  • Regulation of AMPA receptor lateral movements Nature (2002)
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  • None
  • None None (None)
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    Members

    « Researcher »

    BRACHET Anna Researcher anna.brachet@u-bordeaux.fr +33533514732
    CHOQUET Daniel Researcher daniel.choquet@u-bordeaux.fr +33533514715
    COUSSEN Francoise Researcher francoise.coussen-choquet@u-bordeaux.fr +33533514734
    HOSY Eric Researcher eric.hosy@u-bordeaux.fr +33533514730
    SAINLOS Matthieu Researcher matthieu.sainlos@u-bordeaux.fr +33533514731

    « Technical Staff »

    BREILLAT Christelle Technical staff christelle.breillat@u-bordeaux.fr +33533514731
    CHARPENTIER Justine Technical staff justine.charpentier@u-bordeaux.fr +33533514732
    CHEVRIER Nicolas Technical staff nicolas.chevrier@u-bordeaux.fr +33533514733
    Daburon Sophie Technical staff sophie.daburon@u-bordeaux.fr +33533514732
    LEMOIGNE Cécile Technical staff cecile.lemoigne@u-bordeaux.fr +33533514732
    RENOU Ellyn Technical staff ellyn.renou@u-bordeaux.fr +33533514783
    RETAILLEAU Natacha Technical staff natacha.retailleau@u-bordeaux.fr +33533514733

    « Postdoc »

    GETZ Angela Postdoc angela.getz@u-bordeaux.fr +33533514735
    GONZALEZ-CALVO Ines Postdoc ines.gonzalez-calvo@u-bordeaux.fr +33533514700
    JOBIN Marie-Lise Postdoc marie-lise.jobin@u-bordeaux.fr +33533514700
    PECORARO Valeria Postdoc valeria.pecoraro@u-bordeaux.fr +33533514735
    PUENTE Virginia Postdoc virginia.puente@u-bordeaux.fr +33533514735
    ZIEGER Hanna Postdoc hanna.zieger@u-bordeaux.fr +33533514735

    « PhD student »

    BONNET Caroline PhD student caroline.bonnet@u-bordeaux.fr +33533514735
    CAMUS Côme PhD student come.camus@etu.u-bordeaux.fr +33533514749
    NETO Diogo PhD student diogo.neto@u-bordeaux.fr +33533514735
    NOWACKA Agata PhD student agata.nowacka@u-bordeaux.fr +33533514749
    TRIVUNOVIC Ivana PhD student ivana.trivunovic@u-bordeaux.fr +33533514749

    « Alumni & Guests »

    Former group members, followup position

    • Aren borgdorff - 1997-2000, Industry
    • Arnauld Sergé - 1997-2001, Assistant professor Marseille
    • Marianne Renner - 2004-2006, Professor, Paris
    • Caroline Dequidt - 2004-2007, Industry
    • Cécile Bats - 2004-2007, Post-doc, London
    • Martin Heine - 2003-2007, Junior group leader, Magdeburg
    • Enrica Petrini - 2005-2008, Post-doc, Genoa
    • Cezar Tigaret - 2006-2009, Lecturer, Bristol
    • Helge Ewers - 2007-2009, Group leader, Berlin
    • Arnaud Frouin - 2007-2010, Labmanager, NYC
    • Leandro Royer - 2009-2012, Post-doc, Boston
    • Patricio Opazo - 2008-2013, Group leader, Brisbane
    • Jary Delgado - 2009-2013, Post-doc, Chicago
    • Deepak Nair - 2009-2013, Group leader, Bengalor
    • Damien Jullié - 2009-2013, Post-doc, San Francisco
    • Audrey Constal - 2010-2013, Teacher
    • Axel Athane - 2011-2013, Industry
    • Dolors Grillo, 2011-2013, Post-doc, Spain
    • Anne-Sophie Hafner - 2010-2014, Post-doc, Frankfurt
    • Isabelle Gautherau - 2012-2014, Industry
    • Amandine Philippat - 2013-2015, Industry
    • Andrew Penn - 2010-2015, Junior group leader, Sussex
    • Hongyu Zhang - 2010-2015, Post-doc, University of Bergen
    • Estelle Toulme - 2013-2015, Post-doc, Berlin
    • Jennifer Petersen - 2009-2016, Post-doc, NIH
    • Yulia Krapivkina - 2013-2016, Industry
    • Ngoc Van Thi Nhu - 2013-2016, Engineer, Montpellier
    • Emilie Hangen - 2014-2017
    • Ségolène Antoine - 2015-2017, French Industry
    • Sara Crespillo - 2015-2017, Post-doc, Cambridge
    • Célia Michel - 2014-2017, French Industry
    • Benjamin Compans - 2014-2018, Post-doc, London
    • Lucile Pret - 2018, Engineer, London
    • Julia Goncalves – 2015 – 2018, Engineer, Bordeaux Neurocampus
    • Murielle Fevre - 2017-2018
    • Camille Genuer - 2017-2018, Engineer, French Industry
    • Carla Montecinos - 2013-2018
    • Charlotte Rimbault – 2014-2019, Post-doc, Copenhagen
    • Magalie Martineau – 2015-2019, Post-doc, Paris
    • Léa Claverie – 2015 - 2019, UK
    • Florelle Domart - 2016-2019, Post-doc
    • David Perrais - 2011-2020, Group Leader
    • Sylvia Sposini - 2018-2020, Post-doc, Bordeaux
    • Lou Bouit - 2018-2020, Engineer, Bordeaux 

    Guests

    • Raffaella Adami, Pisa - January, June 2001
    • Andres Villu Maricq, Utah - November 2003
    • Radhika Reddy, Worley lab - June 2003
    • Michael Ehlers, Duke University - March, September 2006
    • Renatto Frischknecht, Gundelfinger lab - April 2006, September 2006
    • Laura Andreae, Fine lab - April 2006, November 2006
    • Anna Carbone, Plested Lab - January, April 2012
    • Beulah Leitch, Otago University - October 2013
    • Andrew Plested, FMP Berlin - October 2015, February 2016
    • Nikolaj Riis Christensen, Copenhagen University - June-December 2017
    • Anne Brunet, Stanford University - April-July 2019
    • Pin Wu Liu, Kyoto University Graduate School of Medicine - January 2020
    • Boram Lee, Johannes W. Hell UCDavis - January-June 2020

    Jobs

    PhD position to study synapse nanoscale disorganization in neurodevelopmental disorder models

    The ETN “Synaptic Dysfunction in Neuropsychiatric Disorders” (Syn2Psy) is recruiting an early stage researcher (ESR) to integrate a research project with Eric Hosy and Daniel Choquet @ IINS aimed at understanding the molecular, synaptic, network and behaviour basis of neuropsychiatric disorders.

    Click here to apply.