Publication Date:
2022-05-27
Description:
© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Li, S., Raychaudhuri, S., Lee, S. A., Brockmann, M. M., Wang, J., Kusick, G., Prater, C., Syed, S., Falahati, H., Ramos, R., Bartol, T. M., Hosy, E., & Watanabe, S. Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses. Nature Communications, 12(1), (2021): 677, https://doi.org/10.1038/s41467-021-21004-x.
Description:
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.
Description:
e also thank the Marine Biological Laboratory and their Neurobiology course for supporting the initial set of experiments (course supported by National Institutes of Health grant R25NS063307). S.W. and this work were supported by start-up funds from the Johns Hopkins University School of Medicine, Johns Hopkins Discovery funds, and the National Science Foundation (1727260), the National Institutes of Health (1DP2 NS111133-01 and 1R01 NS105810-01A1) awarded to S.W. S.W. is an Alfred P. Sloan fellow, McKnight Foundation Scholar, and Klingenstein and Simons Foundation scholar. G.K. was supported by a grant from the National Institutes of Health to the Biochemistry, Cellular and Molecular Biology Program of the Johns Hopkins University School of Medicine (T32 GM007445) and is a National Science Foundation Graduate Research Fellow (2016217537). E.H. and T.M.B. are supported by CRCNS-NIH-ANR grant AMPAR-T. The EM ICE high-pressure freezer was purchased partly with funds from an equipment grant from the National Institutes of Health (S10RR026445) awarded to Scot C Kuo.
Repository Name:
Woods Hole Open Access Server
Type:
Article
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