Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses

被引:49
|
作者
Li, Shuo [1 ,2 ]
Raychaudhuri, Sumana [1 ]
Lee, Stephen Alexander [3 ,11 ]
Brockmann, Marisa M. [4 ]
Wang, Jing [5 ]
Kusick, Grant [1 ,6 ]
Prater, Christine [3 ,12 ]
Syed, Sarah [1 ]
Falahati, Hanieh [3 ,13 ]
Ramos, Raul [3 ,14 ]
Bartol, Tomas M. [7 ]
Hosy, Eric [8 ,9 ]
Watanabe, Shigeki [1 ,10 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21218 USA
[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biol & Mol Biol, Baltimore, MD USA
[3] Marine Biol Lab, Neurobiol Course, Woods Hole, MA 02543 USA
[4] Charite, Inst Neurophysiol, Berlin, Germany
[5] ThermoFisher Sci, Hillsboro, OR USA
[6] Johns Hopkins Univ, Sch Med, Biochem Cellular & Mol Biol Grad Program, Baltimore, MD USA
[7] Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA
[8] CNRS, Bordeaux, France
[9] Univ Bordeaux, Interdisciplinary Inst Neurosci, Bordeaux, France
[10] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA
[11] Columbia Univ, Dept Biomed Engn, New York, NY USA
[12] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA
[13] Yale Univ, Sch Med, Dept Neurosci, New Haven, CT USA
[14] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
IONOTROPIC GLUTAMATE RECEPTORS; AMPA RECEPTORS; MOLECULAR-MECHANISMS; POSTSYNAPTIC DENSITY; EXCITATORY SYNAPSES; SYNAPTIC VESICLES; DENDRITIC SPINES; CHANNEL; BLOCK; TRANSMISSION;
D O I
10.1038/s41467-021-21004-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Action potentials induce synchronous and asynchronous release of neurotransmitters. Here, the authors show that the synchronous and asynchronous release sites are aligned with AMPARs and NMDARs, respectively, in mouse hippocampal synapses. This organization allows efficient activation of NMDARs.
引用
收藏
页数:13
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