Macroautophagy (hereafter "autophagy") is a lysosomal degradation pathway that is important for learning and memory, suggesting critical roles for autophagy at the neuronal synapse. Little is known, however, about the molecular details of how autophagy is regulated with synaptic activity. Here, we used live-cell confocal microscopy to define the autophagy pathway in primary hippocampal neurons under various paradigms of synaptic activity. We found that synaptic activity regulates the motility of autophagic vacuoles (AVs) in dendrites. Stimulation of synaptic activity dampens AV motility, whereas silencing synaptic activity induces AV motility. Activity-dependent effects on dendritic AV motility are local and reversible. Importantly, these effects are compartment specific, occurring in dendrites and not in axons. Most strikingly, synaptic activity increases the presence of degradative autolysosomes in dendrites and not in axons. On the basis of our findings, we propose a model whereby synaptic activity locally controls AV dynamics and function within dendrites that may regulate the synaptic proteome.

中文翻译：

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突触活动控制树突中自噬空泡的运动性和功能。

巨自噬（以下称为“自噬”）是一种溶酶体降解途径，对学习和记忆很重要，暗示了自噬在神经突触中的关键作用。然而，关于如何通过突触活性调节自噬的分子细节知之甚少。在这里，我们使用活细胞共聚焦显微镜在各种突触活动范式下定义了原代海马神经元的自噬途径。我们发现突触活动调节树突中自噬泡（AVs）的运动。刺激突触活动抑制AV运动，而沉默突触活动诱导AV运动。依赖于活动的对树突状AV运动的影响是局部的和可逆的。重要的是，这些效应是特定于隔室的，在树突而不是在轴突中发生。最惊人的是 突触活性增加了树突而不是轴突中降解的自溶酶体的存在。根据我们的发现，我们提出了一个模型，其中突触活动局部控制可能调节突触蛋白质组的树突内的AV动态和功能。