Will talk about: A nanoscale view into the dynamic of AMPA receptor organization in synapses
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 theFondation 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.
The spatio-temporal organization of neurotransmitter receptors in the postsynaptic membrane is a fundamental determinant of synaptic transmission and thus information processing by the brain. Ionotropic AMPA glutamate receptors (AMPAR) mediate fast excitatory synaptic transmission in the central nervous system. Using a combination of high resolution single molecule imaging techniques and video-microscopy, we had previously established that AMPARs are not stable in the synapse as thought initially, but undergo continuous entry and exit to and from the post-synaptic density through lateral diffusion.
Using three independent super-resolution imaging methods together with modeling, on both genetically tagged and endogenous receptors, we now demonstrate that, in live hippocampal neurons, AMPAR are highly concentrated inside synapses into a few clusters of around seventy nanometers. AMPAR are stabilized reversibly in these domains and diffuse freely outside them. Nanodomains are themselves dynamic in their shape and position within synapses as they can form and disappear within minutes, although they are for the most part stable for at least up to an hour. These results open the new possibility that glutamatergic synaptic transmission is controlled by the regulation at the nanometer scale of the position and composition of these highly concentrated nanodomains.