Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances
Rapid regulation of vesicle priming explains synaptic facilitation despite heterogeneous vesicle:Ca2+ channel distances
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DOI：
10.7554/elife.51032
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发表时间：
2020-02-20
期刊：
影响因子：
7.7
通讯作者：
Walter, Alexander M.
中科院分区：
文献类型：
--
作者：
Kobbersmed, Janus R. L.;Grasskamp, Andreas T.;Walter, Alexander M.
化学突触传递依赖于Ca 2+诱导的载有递质的囊泡的融合，其与Ca 2+通道的耦合距离决定了突触释放概率和短期可塑性，促进或抑制重复反应。在这里，使用果蝇神经肌肉接头的电子和超分辨率显微镜，我们定量绘制了囊泡：Ca 2+通道耦合距离。这些是非常异质性的，导致突触内广泛的囊泡释放概率。随机模拟发射器释放囊泡放置根据这种分布显示短期可塑性强的约束，特别是便利是难以实现的。我们表明，假设的促进机制通过活性依赖性的变化囊泡释放概率（例如，通过促进融合传感器）产生太少的便利和太多的方差。相反，钙依赖性机制迅速增加可释放囊泡的数量可靠地再现短期可塑性和突触反应的变化。我们建议活性依赖性抑制囊泡非启动或释放位点激活作为新的促进机制。
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.