Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses

Publication date: 27 February 2018
Source:Cell Reports, Volume 22, Issue 9
Author(s): Haowen Liu, Lei Li, Wei Wang, Jihong Gong, Xiaofei Yang, Zhitao Hu
The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca²⁺ channels in triggering spontaneous release at cholinergic and GABAergic synapses. Recordings of the miniature excitatory/inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) showed that UNC-2/CaV2 and EGL-19/CaV1 channels are the two major triggers for spontaneous release. Notably, however, Ca²⁺-independent spontaneous release was observed at GABAergic but not cholinergic synapses. Functional screening led to the identification of hypomorphic unc-64/Syntaxin-1A and snb-1/VAMP2 mutants in which mEPSCs are severely impaired, whereas mIPSCs remain unaltered, indicating differential regulation of these currents at cholinergic and GABAergic synapses. Moreover, Ca²⁺-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca²⁺-dependent and Ca²⁺-independent spontaneous release.

Graphical abstract

Teaser

Liu et al. show that spontaneous release is differentially regulated between cholinergic and GABAergic synapses at the C. elegans NMJ. Ca²⁺-independent spontaneous release is observed in GABAergic synapses and regulated by synaptic proteins such as syntaxin-1A and VAMP2.


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