Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia.
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.
Cell Rep. 2018 Feb 27;22(9):2334-2345. doi: 10.1016/j.celrep.2018.02.023.
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 Ca 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, Ca-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, Ca-independent spontaneous GABA release was nearly abolished in the hypomorphic unc-64 and snb-1 mutants, suggesting distinct mechanisms for Ca-dependent and Ca-independent spontaneous release.
秀丽隐杆线虫的运动由神经肌肉连接处的兴奋性和抑制性神经递质释放来平衡。然而，维持突触传递平衡的分子机制仍然是个谜。在这里，我们研究了电压门控钙通道在触发胆碱能和 GABA 能突触自发性释放中的作用。记录微小兴奋性/抑制性突触后电流（分别为 mEPSC 和 mIPSC）表明 UNC-2/CaV2 和 EGL-19/CaV1 通道是自发性释放的两个主要触发因素。然而，值得注意的是，在 GABA 能突触而不是在胆碱能突触中观察到 Ca 独立的自发性释放。功能筛选导致鉴定出unc-64/Syntaxin-1A 和 snb-1/VAMP2 功能减弱突变体，其中 mEPSC 严重受损，而 mIPSC 保持不变，表明这些电流在胆碱能和 GABA 能突触中受到不同的调节。此外，unc-64 和 snb-1 功能减弱突变体中的 Ca 独立自发性 GABA 释放几乎被消除，表明 Ca 依赖性和 Ca 独立性自发性释放的机制不同。
