Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances

eLife

Susanne Ditlevsen¹  Janus RL Kobbersmed²  Jakob Balslev Sørensen³  Mathias A Böhme⁴  Andreas T Grasskamp⁴  Meida Jusyte⁵  Alexander M Walter⁵ 

[1] Department of Mathematical Sciences, University of Copenhagen, København, Denmark;Department of Mathematical Sciences, University of Copenhagen, København, Denmark;Department of Neuroscience, University of Copenhagen, København, Denmark;Department of Neuroscience, University of Copenhagen, København, Denmark;Molecular and Theoretical Neuroscience, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, FMP im CharitéCrossOver, Berlin, Germany;Molecular and Theoretical Neuroscience, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, FMP im CharitéCrossOver, Berlin, Germany;Einstein Center for Neuroscience, Berlin, Germany;

关键词: synaptic transmission;    short-term plasticity;    vesicular release sites;    ca2+ channels;    mathematical modelling;    stochastic simulation;    D. melanogaster;   

DOI  :  10.7554/eLife.51032

来源: publisher

【 摘 要 】

Chemical synaptic transmission relies on the Ca2+-induced fusion of transmitter-laden vesicles whose coupling distance to Ca2+ channels determines synaptic release probability and short-term plasticity, the facilitation or depression of repetitive responses. Here, using electron- and super-resolution microscopy at the Drosophila neuromuscular junction we quantitatively map vesicle:Ca2+ channel coupling distances. These are very heterogeneous, resulting in a broad spectrum of vesicular release probabilities within synapses. Stochastic simulations of transmitter release from vesicles placed according to this distribution revealed strong constraints on short-term plasticity; particularly facilitation was difficult to achieve. We show that postulated facilitation mechanisms operating via activity-dependent changes of vesicular release probability (e.g. by a facilitation fusion sensor) generate too little facilitation and too much variance. In contrast, Ca2+-dependent mechanisms rapidly increasing the number of releasable vesicles reliably reproduce short-term plasticity and variance of synaptic responses. We propose activity-dependent inhibition of vesicle un-priming or release site activation as novel facilitation mechanisms.

【 授权许可】

CC BY