The
objective of our group is to understand the dynamics of the processes
involved during the formation and plasticity of glutamatergic synapses
in the central nervous system. For this aim, we combine high resolution
imaging, nano-manipulation, neurophysiology and cell biology approaches.
Real
time movement of a single 5 nanometer gold particle bound to an
AMPA receptor diffusing at the surface of a neurite of a cultured
hippocampal neuron tracked using the photothermal imaging technique
Color
coded movie of single molecule images of fluorescently tagged AMPA
receptor (red) diffusing out of a synapse (green).
Main projects
Development of high resolution imaging techniques
in living cells and tissues
STED and PALM imaging to optically localize synaptic components bellow the diffraction limit
Single
molecule imaging to track receptors movements in and out synapses
Multiphoton, FCS, FLIM
and FRET imaging
Dynamic of
glutamate receptor organization
Nanoscale organization of synaptic components
Physiological role of Glutamate receptor trafficking
Regulation of AMPA and NMDA receptor mobility in and out synapses by neuronal activity
Regulation of glutamate receptor mobility by scaffolding proteins Nanoscale organization of synaptic components
Roles of adhesion
proteins in synaptogenesis
Dynamics
of adhesion protein-cytoskeleton interactions
Role
of mechanical constraints in synapse organization
Role
of adhesion proteins in glutamate receptor organization.
Main results
First
real time imaging of glutamate and glycine receptor movements in the
neuronal membrane by single particle tracking (Nature Neuroscience
2001, Nature 2002).
Demonstration
of the dynamic instability of neurotransmitter aggregates (J. Neuroscience
2002).
Role
of intracellular calcium in AMPA receptor stabilization.
Demonstration
that AMPA and NMDA receptors constantly diffuse in and out synapses
Control of this mobility by neuronal activity (EMBO J. 2003 ,
Nature reviews Neuroscience 2003, Nature Neuroscience 2004).
Analyzes
of cadherin-cytoskeleton interactions (J. Cell. Biol. 2002)
Main publications
2009
Petrini, E.M. , Lu, J., Cognet, L., Lounis, B., Ehlers, M.D., and Choquet, D. (2009). Endocytosis and recycling maintain a mobile pool of surface AMPA receptors at synapses required for synaptic potentiation. Neuron 63 , 92-105.
Michaluk, P., Mikasova, L. , Groc, L. , Frischknecht, R., Choquet, D. , and Kaczmarek, L. (2009). Matrix metalloproteinase-9 controls NMDA receptor surface diffusion through integrin beta1 signaling. J Neurosci 29 , 6007-6012.
2008
Heine M, Groc L, Frischknecht R, Béïque JC, Lounis B, Rumbaugh G, Huganir RL, Cognet L, and Choquet D. (2008) Surface Mobility of Postsynaptic AMPARs Tunes Synaptic Transmission Science 320, 201-205
Thoumine, O., Ewers, H., Heine, M., Groc, L., Frischknecht, R., Giannone, G., Poujol, C., Legros, P., Lounis, B., Cognet, L., and Choquet, D. (2008). Probing the dynamics of protein-protein interactions at neuronal contacts by optical imaging. Chem Rev 108, 1565-1587.
Groc, L., Choquet, D., and Chaouloff, F. (2008). The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation. Nat Neurosci 11, 868-870.
Triller, A., and Choquet, D. (2008). New concepts in synaptic biology derived from single-molecule imaging. Neuron 59, 359-374.
2007 and before
Bats C, Groc L, and Choquet D. The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron 53: 719-734, 2007.
Ehlers MD, Heine M, Groc L, Lee MC, and Choquet D. Diffusional Trapping of GluR1 AMPA Receptors by Input-Specific Synaptic Activity. Neuron 54: 447-460, 2007.
Groc, L., Heine, M., Cognet, L., Lounis, B., and Choquet, D. (2006). NMDA receptor surface mobility depends on NR2A-2B subunits. PNAS November 21, , 10.1073, 2006
Groc, C., Heine, M., Cognet, L., Brikley, K., Stephenson, A., Lounis, B., and Choquet, D. (2004). Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors. Nature Neuroscience . Jul;7(7):695-6.
Choquet, D., and Triller, A. (2003). The role of receptor diffusion in the organization of the postsynaptic membrane. Nat Rev Neurosci 4 , 251-265.
Tardin, C., Cognet, L., Bats, C., Lounis, B., and Choquet, D. (2003). Direct imaging of lateral movements of AMPA receptors inside synapses. Embo J 22 , 4656-4665.
Borgdorff, A., and Choquet, D. (2002). Regulation of AMPA receptor lateral movement. Nature 417 , 649–653.
Meier, J., Vannier, C., Sergé, A., Triller, A., and Choquet, D. (2001). Fast and reversible trapping of surface glycine receptors by gephyrin. Nature Neuroscience 4 , 253-260.
Advanced ERC Grant to Daniel Choquet : 
