Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses

Shuo Li, Sumana Raychaudhuri, Stephen Alexander Lee, Marisa M. Brockmann, Jing Wang, Grant Kusick, Christine Prater, Sarah Syed, Hanieh Falahati, Raul Ramos, Tomas M. Bartol, Eric Hosy and Shigeki Watanabe ()
Additional contact information
Shuo Li: Johns Hopkins University, School of Medicine
Sumana Raychaudhuri: Johns Hopkins University, School of Medicine
Stephen Alexander Lee: The Marine Biological Laboratory
Marisa M. Brockmann: Charité Universitätsmedizin
Jing Wang: ThermoFisher Scientific
Grant Kusick: Johns Hopkins University, School of Medicine
Christine Prater: The Marine Biological Laboratory
Sarah Syed: Johns Hopkins University, School of Medicine
Hanieh Falahati: The Marine Biological Laboratory
Raul Ramos: The Marine Biological Laboratory
Tomas M. Bartol: Salk Institute for Biological Studies
Eric Hosy: Centre National de la Recherche Scientifique
Shigeki Watanabe: Johns Hopkins University, School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently.

Date: 2021
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DOI: 10.1038/s41467-021-21004-x

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