Metabolic Regulation of Single Synaptic Vesicle Exo- and Endocytosis in Hippocampal Synapses.
Metabolic Regulation of Single Synaptic Vesicle Exo- and Endocytosis in Hippocampal Synapses.
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海马突触中单个突触小泡胞吐和内吞作用的代谢调节。
DOI：
10.1101/2023.11.08.566236
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Ashrafi,Ghazaleh
中科院分区：
文献类型：
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作者：
Myeong,Jongyun;Stunault,MarionI;Klyachko,VitalyA;Ashrafi,Ghazaleh
长期以来，葡萄糖一直被认为是突触功能的主要能量来源。然而，目前还不清楚替代燃料，如乳酸盐/丙酮酸盐，在多大程度上有助于为突触传递提供动力。通过检测海马突触中的单个释放事件，我们发现线粒体ATP产生调节由单个动作电位诱发的活动区（AZ）内的基础囊泡释放概率和释放位置。线粒体抑制转移囊泡释放更接近AZ中心，并通过增加超快内吞作用的发生来改变囊泡回收的效率。此外，我们发现，终端可以使用氧化燃料，以维持囊泡循环过程中的列车活动。线粒体是稀疏分布沿着海马轴突，我们发现，终端含有线粒体显示增强囊泡释放和再摄取过程中的高频率列车。我们的研究结果表明，线粒体不仅调节突触传递的几个基本特征，但也可能有助于调制短期突触可塑性。
Glucose has long been considered a primary energy source for synaptic function. However, it remains unclear to what extent alternative fuels, such as lactate/pyruvate, contribute to powering synaptic transmission. By detecting individual release events in hippocampal synapses, we find that mitochondrial ATP production regulates basal vesicle release probability and release location within the active zone (AZ), evoked by single action potentials. Mitochondrial inhibition shifts vesicle release closer to the AZ center and alters the efficiency of vesicle retrieval by increasing the occurrence of ultrafast endocytosis. Furthermore, we uncover that terminals can use oxidative fuels to maintain the vesicle cycle during trains of activity. Mitochondria are sparsely distributed along hippocampal axons, and we find that terminals containing mitochondria display enhanced vesicle release and reuptake during high-frequency trains. Our findings suggest that mitochondria not only regulate several fundamental features of synaptic transmission but may also contribute to modulation of short-term synaptic plasticity.