Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.376111v1?rss=1 Authors: Lee, B. J., Yang, C. H., Lee, S. Y., Lee, S.-H., Kim, Y., Ho, W.-K. Abstract: Neurotransmitter release occurs either synchronously to action potentials or spontaneously, yet whether molecular machineries underlying evoked and spontaneous release are identical, especially whether voltage-gated calcium channels (VGCCs) can trigger spontaneous events has been in debate. To elucidate this issue, we characterized Ca2+ dependency of miniature excitatory postsynaptic currents (mEPSCs) in autaptic cultured hippocampal neurons. We found that 58 % mEPSC frequency was dependent on extracellular Ca2+ ([Ca2+]o), and Ca2+ cooperativity of spontaneous release was comparable to that of evoked release. Moreover, most (> 90 %) of [Ca2+]o-dependent mEPSCs was attributable to VGCCs. Coupling distance between VGCCs and Ca2+ sensors was estimated as tight for both spontaneous and evoked release (~22 nm). In hippocampal slices, VGCC-dependence on spontaneous release was also observed, but to a different extent, at different areas and ages. At the calyx of Held synapses, mEPSCs showed VGCC-dependence in type 1 mature synapses where VGCCs and Ca2+ sensors are tightly coupled, but not in immature synapses. These data strongly suggest that the distance between VGCCs and Ca2+ sensors is the key factor to determine VGCC dependence of spontaneous release. Copy rights belong to original authors. Visit the link for more info