Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission
Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission
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DOI：
10.1523/jneurosci.1571-19.2019
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发表时间：
2020-01-02
影响因子：
5.3
通讯作者：
Takahashi, Tomoyuki
中科院分区：
文献类型：
--
作者：
Babu, Lashmi Piriya Ananda;Wang, Han-Ying;Takahashi, Tomoyuki
细胞骨架丝，如微管（MT）和丝状肌动蛋白（F-肌动蛋白）动态支持细胞的结构和功能。在中央突触前末梢，F-肌动蛋白表达沿着释放边缘，据报道发挥多种功能的作用，但轴突MT是否延伸到终端深处，发挥任何生理作用仍然存在争议。在任何性别的大鼠，共聚焦和高分辨率显微镜显示，MT进入深入突触前终末sleep和部分共定位与突触囊泡（SV）的子集的杯。电生理学分析表明，解聚的MT特异性延长的慢恢复时间的组成部分EPSCs从短期抑郁症诱导的一系列高频刺激，而解聚的F-肌动蛋白特异性延长的快速恢复的组成部分。在同时突触前和突触后动作电位记录中，MT或F-肌动蛋白的解聚显著损害了高频神经传递的保真度。我们的结论是，MT和F-肌动蛋白差异有助于慢和快SV补充，从而维持高频率的神经传递。
Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission.