Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules

Adam Fekete, Yukihiro Nakamura, Yi Mei Yang, Stefan Herlitze, Melanie D. Mark, David A. DiGregorio, Lu Yang Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Synaptic heterogeneity is widely observed but its underpinnings remain elusive. We addressed this issue using mature calyx of Held synapses whose numbers of bouton-like swellings on stalks of the nerve terminals inversely correlate with release probability (Pr). We examined presynaptic Ca 2+ currents and transients, topology of fluorescently tagged knock-in Ca 2+ channels, and Ca 2+ channel-synaptic vesicle (SV) coupling distance using Ca 2+ chelator and inhibitor of septin cytomatrix in morphologically diverse synapses. We found that larger clusters of Ca 2+ channels with tighter coupling distance to SVs elevate Pr in stalks, while smaller clusters with looser coupling distance lower Pr in swellings. Septin is a molecular determinant of the differences in coupling distance. Supported by numerical simulations, we propose that varying the ensemble of two morphological modules containing distinct Ca 2+ channel-SV topographies diversifies Pr in the terminal, thereby establishing a morpho-functional continuum that expands the coding capacity within a single synapse population.

Original languageEnglish (US)
Article number826
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
This work is supported by Operating Grants from the Canadian Institutes of Health Research (MOP-77610, MOP-81159, MOP-14692, VIH-105441), Natural Sciences and Engineering Research Council of Canada (Discovery Grant, RGPIN-2017-06665) and Canada Research Chair to L.Y.W.; D.A.D. is supported by the Centre National de la Recherche Scientifique, Fondation pour la Recherche Medicale and the Agence Nationale de la Recherche (ANR-2010-BLANC-1411 and ANR-13-BSV4-0016), and his laboratory is a member of the Bio-Psy Laboratory of Excellence. Y.N. was supported by the Japan Society for the Promotion of Science (KAKENHI Grant JP17K07064).

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