Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses
Year: 2020
Type: article
Abstract: The nanoscale co-organization of neurotransmitter receptors facing presynaptic release sites is a fundamental determinant of their coactivation and of synaptic physiology. At excitatory synapses, how endogenous AMPARs, NMDARs, and mGluRs are co-organized inside the synapse and their respective activation during glutamate release are still unclear. Combining single-molecule superresolution microscopy, electrophysiology, and modeling, we determined the average quantity of each glutamate receptor type, their nanoscale organization, and their respective activation. We observed that NMDARs form a unique cluster mainly at the center of the PSD, while AMPARs segregate in clusters surrounding the NMDARs. mGluR5 presents a different organization and is homogenously dispersed at the synaptic surface. From these results, we build a model predicting the synaptic transmission properties of a unitary synapse, allowing better understanding of synaptic physiology.
Institutions: Centre National de la Recherche Scientifique, Université de Bordeaux, Institut Interdisciplinaire de Neuroscience, Salk Institute for Biological Studies, Howard Hughes Medical Institute, Inserm, Bordeaux Imaging Center, Institut de Biologie Structurale, Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique, Université Grenoble Alpes
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Role of the Planar Cell Polarity (PCP) signaling in the dynamic organization of synapses and the integration of synaptic information: from basic mechanisms to patho-physiological consequences, New light-driven channels and transporters for optogenetics, Canaux ioniques d'intérêt thérapeutique, High Performance Computing for Multiscale Modeling of Biological Systems, University of Bordeaux Neurocampus Graduate School, CRCNS: Regulating AMPAR trapping and desensitization in the postsynaptic density
OpenAlex ID: W3033163957