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

Abstract

The nanoscale co -organization of neurotransmitter receptors fac- ing 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 dis- persed 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.