Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses
Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses
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DOI：
10.1016/j.celrep.2018.02.023
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Hu, Zhitao
中科院分区：
文献类型：
--
作者：
Liu, Haowen;Li, Lei;Hu, Zhitao
线虫的运动是通过神经肌肉接头释放的兴奋性和抑制性神经递质来平衡的。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 Ca2+ 通道在触发胆碱能和 GABA 能突触自发释放中的功能。微型兴奋性/抑制性突触后电流（分别为 mEPSC 和 mIPSC）的记录表明，UNC-2/CaV2 和 EGL-19/CaV1 通道是自发释放的两个主要触发器。然而值得注意的是，在 GABA 突触而非胆碱能突触中观察到了 Ca2+ 独立的自发释放。功能筛选导致鉴定出亚等位性 unc-64/Syntaxin-1A 和 snb-1/VAMP2 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 能突触处的差异调节。此外，在亚等位性unc-64和snb-1突变体中，不依赖Ca2+的自发GABA释放几乎被消除，这表明Ca2+依赖和不依赖Ca2+的自发释放有不同的机制。
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.