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Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules
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 Ca2+ currents and transients, topology of fluorescently tagged knock-in Ca2+ channels, and Ca2+ channel-synaptic vesicle (SV) coupling distance using Ca2+ chelator and inhibitor of septin cytomatrix in morphologically diverse synapses. We found that larger clusters of Ca2+ 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 Ca2+ channel-SV topographies diversifies Pr in the terminal, thereby establishing a morpho-functional continuum that expands the coding capacity within a single synapse population.
Cited literature [79 references]
https://hal-cnrs.archives-ouvertes.fr/hal-02378980
Contributor : David Digregorio <>
Submitted on : Monday, January 6, 2020 - 5:49:13 PM
Last modification on : Monday, January 13, 2020 - 5:08:18 PM
Long-term archiving on: : Tuesday, April 7, 2020 - 11:25:06 PM
Contributor : David Digregorio <>
Submitted on : Monday, January 6, 2020 - 5:49:13 PM
Last modification on : Monday, January 13, 2020 - 5:08:18 PM
Long-term archiving on: : Tuesday, April 7, 2020 - 11:25:06 PM
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s41467-019-08452-2.pdf
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