GluR2 endocytosis-dependent protein degradation in the amygdala mediates memory updating
GluR2 endocytosis-dependent protein degradation in the amygdala mediates memory updating
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DOI：
10.1038/s41598-019-41526-1
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发表时间：
2019-03-26
影响因子：
4.6
通讯作者：
Helmstetter, Fred J.
中科院分区：
文献类型：
--
作者：
Ferrara, Nicole C.;Jarome, Timothy J.;Helmstetter, Fred J.
在巴甫洛夫恐惧条件反射过程中习得的联想是快速而持久的，为研究长期记忆的形成、储存和检索提供了一个理想的模型。在检索过程中，这些记忆会“不稳定”，变得不稳定，允许短暂的“再巩固”窗口，在此期间记忆可以更新，这表明再巩固可能是一个有吸引力的目标，用于修改与过去创伤经历有关的记忆。这种记忆不稳定过程是由杏仁核中的蛋白质降解和glur2内吞作用调节的。然而，目前尚不清楚杏仁核中检索依赖的glur2内吞作用是否对将新信息纳入记忆痕迹至关重要。我们研究了在记忆检索过程中添加新信息是否需要glur2内吞作用来修改原始记忆。在检索过程中出现两次较弱强度的足部冲击导致GluR2内吞依赖性的恐惧反应增加，这表明原始记忆的修改。这种恐惧表达的增加与杏仁核中相同细胞群中蛋白质降解和zif268表达的增加有关，表明不稳定过程和细胞活性增加，并且在glur2内吞作用阻断后两者都消失了。这些数据表明，杏仁核中含有glur2的AMPA受体的内吞作用通过调节细胞的不稳定和活性来调节提取诱导的创伤事件记忆的强化。
Associations learned during Pavlovian fear conditioning are rapidly acquired and long lasting, providing an ideal model for studying long-term memory formation, storage, and retrieval. During retrieval, these memories can "destabilize" and become labile, allowing a transient "reconsolidation" window during which the memory can be updated, suggesting that reconsolidation could be an attractive target for the modification of memories related to past traumatic experiences. This memory destabilization process is regulated by protein degradation and GluR2-endocytosis in the amygdala. However, it is currently unknown if retrieval-dependent GluR2-endocytosis in the amygdala is critical for incorporation of new information into the memory trace. We examined whether the addition of new information during memory retrieval required GluR2-endocytosis to modify the original memory. The presentation of two foot shocks of weaker intensity during retrieval resulted in GluR2 endocytosis-dependent increase in fear responding on a later test, suggesting modification of the original memory. This increase in fear expression was associated with increased protein degradation and zif268 expression in the same population of cells in the amygdala, indicating increased destabilization processes and cellular activity, and both were lost following blockade of GluR2-endocytosis. These data suggest that the endocytosis of GluR2-containing AMPA receptors in the amygdala regulates retrieval-induced strengthening of memories for traumatic events by modulating cellular destabilization and activity.