Dynamic Organization and Function of Synapses
"Progress in science depends on new techniques, new discoveries and new ideas, probably in that order"
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 use of high resolution imaging to study the trafficking of neurotransmitter receptors in neural cells. 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. He has been awarded two ERC advanced grants in 2008 and 2013.
The team develops several research topics, combining neuroscience, physics and chemistry in order to unravel the dynamics of multimolecular complexes and their role in synaptic transmission.
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:
a) trafficking of neuronal molecules such as glutamate receptors is highly dynamic,
b) regulations of protein-protein interactions play key roles in the control of this trafficking at different steps, including lateral diffusion, endo and exocytosis,
c) 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.
The general line of research of the Chemical Biology axis consists in exploiting techniques from chemistry, biophysics and protein engineering in order to develop novel tools and approaches to elucidate biological processes involved in the basis of synaptic transmission.
The group picture
Key Selected Publications
Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95 (2013).
Nair, D.#, Hosy, E.#, Petersen, J. D., Constals, A., Giannone, G., Choquet, D.*, Sibarita, J.B.*
J Neuroscience 33, 13204-13224. #Co first-authors. *Co-last authors.
Caged mono- and divalent ligands for light-assisted disruption of PDZ domain-mediated interactions (2013).
Sainlos M, Iskenderian-Epps WS, Olivier NB, Choquet D, Imperiali B
Neurexin-1beta Binding to Neuroligin-1 Triggers the Preferential Recruitment of PSD-95 versus Gephyrin through Tyrosine Phosphorylation of Neuroligin-1. (2013)
Giannone G, Mondin M, Grillo-Bosch D, Tessier B, Saint-Michel E, Czondor K, Sainlos M, Choquet D, Thoumine O
Cell Rep 3:1996-2007.
CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors (2013).
Carta M, Opazo P, Veran J, Athané A, Choquet D, Coussen F, Mulle C.
EMBO J. 32, 496-510.
Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule (2012).
Zhang H, Etherington LA, Hafner AS, Belelli D, Coussen F, Delagrange P, Chaouloff F, Spedding M, Lambert JJ, Choquet D*, Groc L*.
Mol Psychiatry. 2012 Jun 26. * Co-last authors.
Opazo P, Choquet D (2011).
A three-step model for the synaptic recruitment of AMPA receptors.
Mol Cell Neurosci 46, 1-8.
Sainlos M, Tigaret C, Poujol C, Olivier NB, Bard L, Breillat C, Thiolon K, Choquet D*, Imperiali B* (2011).
Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization.
Nat Chem Biol 7, 81-91. * Co-last authors.
Opazo P, Labrecque S, Tigaret CM, Frouin A, Wiseman PW, De Koninck P, Choquet D (2010).
CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin.
Neuron 67, 239-252.
Petrini EM, Lu J, Cognet L, Lounis B, Ehlers MD, Choquet D (2009).
Endocytosis and recycling maintain a mobile pool of surface AMPA receptors at synapses required for synaptic potentiation.
Neuron 63, 92-105.
#Frischknecht R, #Heine M, Perrais D, Seidenbecher CI, *Choquet D, *Gundelfinger ED (2009).
Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity.
Nature Neuroscience 12, 897-904. #Co-first authors. * Co-last authors.
Heine M, Groc L, Frischknecht R, Beique JC, Lounis B, Rumbaugh G, Huganir RL, Cognet L, Choquet D (2008).
Surface mobility of postsynaptic AMPARs tunes synaptic transmission.
Science 320, 201-205.
Bats C, Groc L, Choquet D (2007).
The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking.
Neuron 53, 719-734.
Ehlers MD, Heine M, Groc L, Lee MC, Choquet D (2007).
Diffusional Trapping of GluR1 AMPA Receptors by Input-Specific Synaptic Activity.
Neuron 54, 447-460.
Merrifield* CJ, Perrais* D, Zenisek D (2005).
Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells.
Cell 121, 593-606. *Equal contributors.
Tardin C, Cognet L, Bats C, Lounis B, Choquet D (2003).
Direct imaging of lateral movements of AMPA receptors inside synapses.
Embo J 22, 4656-4665.
Borgdorff AJ, Choquet D (2002).
Regulation of AMPA receptor lateral movements.
Nature 417, 649-653.