Pathophysiology of synaptic transmission
par- 4 mai 2011
Group Leader : Laurent FAGNI, DR1 CNRS
One of the most important challenge of this XXIst century will be the discovery of efficient therapies against neurological disorders. To this end, a reasonable strategy is to improve our understanding of the brain in order to identify best therapeutic targets. We follow this strategy by searching for molecular determinants that control the formation, function and plasticity of synaptic contacts, under physiological and pathological conditions. More specifically, we focus on the nature and functional role of synaptic proteins involved in the targeting, assembly and signalling of glutamate receptors. We pay a special attention to factors able to affect synaptic functions in the most prevalent neurological diseases : epilepsies, mental retardation and neurodegenerative diseases.
Moutin E, Raynaud F, Roger J, Pellegrino E, Homburger V, Bertaso F, Ollendorff V, Bockaert J, Fagni L, Perroy J. Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability. J Cell Biol. 2012, 198:251-263.
Moutin, E., Raynaud, F., Fagni, L., Perroy, J. GKAP-DLC2 interaction organizes postsynaptic scaffold complex to enhance synaptic NMDA activity. J. Cell Sci, 2012, 125:2030-40.
Burguière , De Bundel D, Valjent E, Roger J, Smolders I, Fagni L, Perroy J. Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture. Neuropharmacology. 2012 (in press).
Durand, C. M., Perroy, J., Loll, F., Perrais, D., Fagni, L., Bourgeron, T., Montcouquiol, M., Sans, N. SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism. Molecular Psychiatry, 2011, Open, 1-14
Bertaso F, Zhang C, Scheschonka A, de Bock F, Fontanaud P, Marin P, Huganir RL, Betz H, Bockaert J, Fagni L, Lerner-Natoli M. PICK1 uncoupling from mGluR7a causes absence-like seizures. Nat. Neurosci. 2008, 111 : 940-948