Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting
Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting
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DOI：
10.1126/science.aav1483
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发表时间：
2019-01-04
期刊：
影响因子：
56.9
通讯作者：
Dean, Camin
中科院分区：
文献类型：
--
作者：
Awasthi, Ankit;Ramachandran, Binu;Dean, Camin
遗忘很重要。没有它，在不断变化的环境中获得的记忆的相对重要性就会丧失。我们发现 synaptotagmin-3 (Syt3) 定位于突触后内吞区，并响应刺激而从突触质膜上去除 AMPA 受体。 AMPA 受体内化、长时程抑制 (LTD) 和突触强度长时程增强 (LTP) 衰减需要 Syt3 的钙感应，并通过 Syt3 敲除而消除。在空间记忆任务中，Syt3 被敲除的小鼠学习正常，但表现出缺乏遗忘。破坏 Syt3：野生型背景中的 GluA2 结合模仿了 LTP 衰变的缺乏和遗忘的缺乏，并且这些效应在 Syt3 敲除背景中被封闭。我们的研究结果为 Syt3 内化 AMPA 受体以抑制突触强度并促进遗忘的分子机制提供了证据。
Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3: GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.