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

PNAS (Proceedings of the National Academy of Sciences) (2020)

J. Goncalves, T.M. Bartol, C. Camus, F. Levet, A.P. Menegolla, T.J. Sejnowski, J.B. Sibarita, M. Vivaudou, D. Choquet, E. Hosy

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.