Contact: Daniel CHOQUET
Tel. (+33)5 33 51 47 15
The AMPAR Diffusion and Synaptic Plasticity axis is the historic research theme of the team Dynamics of Synapse Organization and Function group .
This activity is directly supervised by Daniel Choquet (DRCE, senior researcher) and currently involves Tiago Campelo (PhD Student), Franzisca Scharkowski (Post-doctoral fellow), Hajer El Oussini (Post-doctoral fellow), Christelle Breillat (Research engineer) and Natacha Retailleau (Assistant Engineer). We demonstrated that AMPARs diffuse at the neuronal surface and constantly exchange between synaptic and extrasynaptic locations by Brownian diffusion (Bordgorff & Choquet, Nature 2002), that this diffusion is highly regulated by neuronal activity (Opazo et al. Neuron 2010, Hafner et al., Neuron 2015, Constals et al. Neuron 2015) and that this diffusion can modulate short term plasticity (Heine et al. Science 2008). Based on these initial findings, we have postulated that AMPAR surface diffusion and it’s regulation are key factors to regulate AMPAR numbers at synaptic sites. This has led us to suggest that AMPAR surface diffusion and regulated stabilization through interaction with scaffolding proteins is a fundamental mechanism at play during various forms of synaptic plasticity. To test this hypothesis, we are developing complementary topics:
We use various technics such as slice electrophysiology, cell biology coupled with high resolution microscopy and video-microscopy.
This activity is currently funded by the ERC "ADOS " 2014-2018: D. Choquet (Coord). (Ampa receptor Dynamic Organization and Synaptic transmission in health and disease).
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
CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
Carta M, Opazo P, Veran J, Athané A, Choquet D, Coussen F, Mulle C. EMBO J. 2013 Feb
Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule.
Zhang, H., Etherington, L., Hafner, A.S., Belelli, D., Coussen, F., Delagrange, P., Chaouloff, F., Spedding, M., Lambert, J., Choquet, D. and Groc, L. (2012). Molecular Psychiatry, June 26, 1-14.
Surface mobility of postsynaptic AMPARs tunes synaptic transmission.
Heine M, Groc L, Frischknecht R, Béïque JC, Lounis B, Rumbaugh G, Huganir RL, Cognet L, Choquet D. (2008). Science, Apr 11;320(5873):201-5
Regulation of AMPA receptor lateral movements.
Borgdorff AJ, Choquet D. (2002). Nature, 2002 Jun 6;417(6889):649-53.