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; Shigeki Watanabe

doi:10.1038/s41467-021-21004-x

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, Shigeki Watanabe

School of Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Article number	677
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21004-x
State	Published - Dec 2021

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses",

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.",

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doi = "10.1038/s41467-021-21004-x",

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T1 - Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses

AU - Li, Shuo

AU - Raychaudhuri, Sumana

AU - Lee, Stephen Alexander

AU - Brockmann, Marisa M.

AU - Wang, Jing

AU - Kusick, Grant

AU - Prater, Christine

AU - Syed, Sarah

AU - Falahati, Hanieh

AU - Ramos, Raul

AU - Bartol, Tomas M.

AU - Hosy, Eric

AU - Watanabe, Shigeki

PY - 2021/12

Y1 - 2021/12

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AB - 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.

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Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses

Abstract

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