How AMPA receptor dynamics contribute to tune synaptic plasticity and learning - Daniel Choquet

 

Daniel Choquet, PhD

Director of Interdisciplinary Institute for Neuroscience
the Bordeaux Imaging Center, CNRS
Bordeaux University

Host: Robert Malenka

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Abstract

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 superresolution imaging and tracking techniques, we have established that AMPARs are not all stable in the synapse as thought initially, but in large part undergo continuous entry and exit to and from the post-synaptic density through lateral diffusion. The other fraction of AMPAR are highly concentrated inside synapses into a few clusters of around seventy nanometers. These results have opened 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. The dynamic exchange of AMPAR within the PSD and between synaptic and extrasynaptic sites is highly regulated by neuronal activity. We have demonstrated that AMPAR conformation strongly impacts their mobility, desensitized receptors being more mobile than naïve ones. This property likely explains how post-synaptic AMPAR receptor mobility can regulate short term synaptic plasticity, a feature previously ascribed to pre-synaptic mechanisms. Recently, using new methods to exogenously control AMPAR surface diffusion, we have demonstrated that AMPAR surface diffusion directly controls the establishment of long term synaptic plasticity. We will now present a series of new results that 1) establish a link between regulation of AMPAR surface diffusion and changes in short term plasticity during Long Term Depression, 2) expand the role of AMPAR surface diffusion to synaptic plasticity in vivo and 3) present how controlling AMPAR surface trafficking can provide insight into the implication of synaptic plasticity in various learning paradigms.

Curriculum vitae

Related papers

[1] A. C. Penn, C. L. Zhang, F. Georges, L. Royer, C. Breillat, E. Hosy, J. D. Petersen, Y. Humea, D. Choquet. Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors. Nature volume 549, pages 384–388 (21 September 2017). DOI:10.1038/nature23658   [2] Audrey Constals, Andrew C. Penn, ..., Eric Hosy, Daniel Choquet. Glutamate-Induced AMPA Receptor Desensitization Increases Their Mobility and Modulates Short-Term Plasticity through Unbinding from Stargazin. Constals et al., 2015, Neuron 85, 1–17, February 18, 2015. DOI: 10.1016/j.neuron.2015.01.012