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


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.

SUBMITTER: Goncalves J 

PROVIDER: S-EPMC7321977 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Goncalves Julia J   Bartol Tomas M TM   Camus Côme C   Levet Florian F   Menegolla Ana Paula AP   Sejnowski Terrence J TJ   Sibarita Jean-Baptiste JB   Vivaudou Michel M   Choquet Daniel D   Hosy Eric E  

Proceedings of the National Academy of Sciences of the United States of America 20200608 25


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 t  ...[more]

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