关键词: ATP CP: Metabolism CP: Neuroscience glycolysis hippocampal neuron mitochondria nerve terminal synapse synaptic transmission

Mesh : Synaptic Vesicles / metabolism Endocytosis / physiology Animals Hippocampus / metabolism Synapses / metabolism Mitochondria / metabolism Exocytosis / physiology Synaptic Transmission / physiology Rats Adenosine Triphosphate / metabolism Male Action Potentials / physiology

来  源:   DOI:10.1016/j.celrep.2024.114218   PDF(Pubmed)

Abstract:
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.
摘要:
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,目前尚不清楚替代燃料的程度,如乳酸/丙酮酸盐,有助于突触传递。通过检测海马突触中的个体释放事件,我们发现线粒体ATP的产生调节基底囊泡的释放概率和活性区(AZ)内的释放位置,由单一动作电位诱发。线粒体抑制使囊泡释放更靠近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来维持活动列车期间的囊泡循环。线粒体沿海马轴突稀疏分布,我们发现含有线粒体的末端在高频训练中显示出增强的囊泡释放和再摄取。我们的发现表明,线粒体不仅调节突触传递的几个基本特征,而且还可能有助于调节短期突触可塑性。
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