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Co-organization and coactivation of AMPAR, NMDAR, and mGluR - PNAS, June 2020

Co-organization and coactivation of AMPAR, NMDAR, and mGluR - PNAS, June 2020

Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses

The nanoscale co-organization of neurotransmitter receptors fac-ing presynaptic release sites is a fundamental determinant of theircoactivation and of synaptic physiology. At excitatory synapses,how endogenous AMPARs, NMDARs, and mGluRs are co-organizedinside the synapse and their respective activation during glutamaterelease are still unclear. Combining single-molecule superresolutionmicroscopy, electrophysiology, and modeling, we determined theaverage quantity of each glutamate receptor type, their nanoscaleorganization, and their respective activation. We observed thatNMDARs 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 dis-persed at the synaptic surface. From these results, we build a modelpredicting the synaptic transmission properties of a unitary synapse,allowing better understanding of synaptic physiology.

Co-organization of the various glutamate receptors. Dual-color dSTORM imaging is represented with Coloc-Tesseler software of NR1-containing NMDAR and GluA2-containing AMPAR (A) and mGluR5-containing mGluR and GluA2-containing AMPAR (B). For A and B, the Upper Left panel represents the 532 nm channel, and the Lower Left panel represents the 647 nm channel; the overlay is shown at the center, and synapses are zoomed in the Right. In A it appears clearly that the NMDAR cluster (in green) is surrounded by one to two AMPAR clusters (in red). C and E represent the distribution of the cluster centroid–to–cluster centroid distance for AMPAR/NMDAR (C) and AMPAR/mGluR (E). D is the distribution of the AMPAR domains around the NMDAR clusters (located at the origin of the graph). The x and y coordinates are expressed in nanometers. The larger AMPAR cluster distance is projected by rotation on the positive y axis (blue dots); the other cluster coordinates are obtained by applying similar rotation vectors (orange dots). Data represent 91 individuals synapses and 325 AMPAR clusters. (F) Because mGluR does not present clustering, its overlapping with AMPAR is not relevant, so we represent the density of mGluR single objects on the dendrite and in the area enriched in AMPAR. ***P<0.001.

Authors: Julia Goncalves, Tomas M. Bartol, Côme Camus, Florian Levet, Ana Paula Menegolla,Terrence J. Sejnowski, Jean-Baptiste Sibarita, Michel Vivaudou, Daniel Choquet and Eric Hosy

- Publication in PNAS, June 8, 2020
- Contact: Eric Hosy

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