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

Adam Fekete (1, 2) , Yukihiro Nakamura (3) , Yi-Mei Yang (1) , Stefan Herlitze (4) , Melanie D. Mark (4) , David Digregorio (5) , Lu-Yang Wang (1)

1 SickKids - The Hospital for sick children [Toronto]
2 University of Toronto
3 The Jikei University School of Medicine
4 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
5 Imagerie dynamique du Neurone

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.

Domaines: Neurobiologie

Adam Fekete, Yukihiro Nakamura, Yi-Mei Yang, Stefan Herlitze, Melanie D. Mark, et al.. Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules. Nature Communications, 2019, 10 (1), pp.826. ⟨10.1038/s41467-019-08452-2⟩. ⟨hal-02378980⟩