Differentially poised vesicles underlie fast and slow components of release at single synapses
Differentially poised vesicles underlie fast and slow components of release at single synapses
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DOI：
10.1085/jgp.201912523
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发表时间：
2020-05-01
影响因子：
3.8
通讯作者：
Trigo, Federico F.
中科院分区：
文献类型：
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作者：
Blanchard, Kris;de San Martin, Javier Zorrilla;Trigo, Federico F.
在几种类型的中枢哺乳动物突触中，持续的突触前刺激导致突触囊泡释放的两个组成部分的序列，反映了快速释放池（FRP）和缓慢释放池（SRP）的连续贡献。先前的工作已经表明，在通过强刺激的共同耗尽之后，FRP和SRP以不同的动力学恢复。然而，目前还不清楚是否有任何操作可能导致选择性增强FRP或SRP。为了解决这个问题，我们进行了局部突触前钙uncaging在单个突触前静脉曲张的小脑中间神经元。这些静脉曲张通常在突触后中间神经元上形成“简单突触”，涉及单个活性区内的几个（一到六个）对接/释放位点。我们发现，强大的uncaging激光脉冲引起两个阶段的释放与时间常数类似的1毫秒（FRP释放）和类似的20毫秒（SRP释放）。当在动作电位诱发的囊泡释放之前解除包囊时，SRP释放的程度特异性增强。我们解释这种影响反映了两步释放（对接，然后释放）的可能性增加后，消除对接突触囊泡的动作电位诱发释放。与此相反，阈下激光诱发的突触前静脉曲张的钙离子升高导致FRP释放的增强。我们解释这后一种效果，反映了一个增加的概率占用的对接网站后，阈下钙增加。总之，快速和缓慢的释放组件可以通过特定的突触前操纵增强。我们的研究结果有影响的机制对接网站的补充和调节突触反应，特别是以下激活的离子型突触前受体。
In several types of central mammalian synapses, sustained presynaptic stimulation leads to a sequence of two components of synaptic vesicle release, reflecting the consecutive contributions of a fast-releasing pool (FRP) and of a slow-releasing pool (SRP). Previous work has shown that following common depletion by a strong stimulation, FRP and SRP recover with different kinetics. However, it has remained unclear whether any manipulation could lead to a selective enhancement of either FRP or SRP. To address this question, we have performed local presynaptic calcium uncaging in single presynaptic varicosities of cerebellar interneurons. These varicosities typically form "simple synapses" onto postsynaptic interneurons, involving several (one to six) docking/release sites within a single active zone. We find that strong uncaging laser pulses elicit two phases of release with time constants of similar to 1 ms (FRP release) and similar to 20 ms (SRP release). When uncaging was preceded by action potential-evoked vesicular release, the extent of SRP release was specifically enhanced. We interpret this effect as reflecting an increased likelihood of two-step release (docking then release) following the elimination of docked synaptic vesicles by action potential-evoked release. In contrast, a subthreshold laser-evoked calcium elevation in the presynaptic varicosity resulted in an enhancement of the FRP release. We interpret this latter effect as reflecting an increased probability of occupancy of docking sites following subthreshold calcium increase. In conclusion, both fast and slow components of release can be specifically enhanced by certain presynaptic manipulations. Our results have implications for the mechanism of docking site replenishment and the regulation of synaptic responses, in particular following activation of ionotropic presynaptic receptors.