Memory accuracy predicts hippocampal mTOR pathway activation following retrieval of contextual fear memory.
Memory accuracy predicts hippocampal mTOR pathway activation following retrieval of contextual fear memory.
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DOI：
10.1002/hipo.22140
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发表时间：
2013-09
期刊：
影响因子：
3.5
通讯作者：
Helmstetter, Fred J.
中科院分区：
文献类型：
--
作者：
Gafford, Georgette M.;Parsons, Ryan G.;Helmstetter, Fred J.
先前的研究表明，依赖于海马体的记忆经历了一个系统巩固过程，最近的记忆存储在海马体中，而较旧的记忆独立于海马体，而是依赖于皮层区域。解释这些研究的一个问题是，随着训练事件和测试之间的时间推移，对背景刺激的记忆会减弱，而旧的记忆往往不那么详细，这使得很难确定海马体中的记忆存储是否与年龄或记忆的准确性有关。已知哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的活性对于控制初始学习后记忆巩固和检索后记忆再巩固所必需的蛋白质翻译是重要的。我们测试了背景恐惧条件反射后1、10或36天背海马（DH）和前扣带皮层（ACC）中背景恐惧记忆恢复后p70s6激酶（p70s6K）（mTOR信号通路的关键组分）是否被激活。我们还测试了在训练后36天，加强对背景刺激的记忆是否会改变这些结构中的p70s6K磷酸化。我们发现，在标准的训练条件下检索最近形成的记忆最初是精确的，涉及DH。随着时间的推移，它会失去细节，变得独立于DH，并依赖于ACC。在随后的实验中，我们通过预先暴露于训练环境来保留旧记忆的准确性。我们发现，远程记忆仍然涉及DH在动物预先曝光。这些数据支持这样一种观点，即无论年龄大小，详细的记忆都取决于DH。
Prior work suggests hippocampus-dependent memory undergoes a systems consolidation process such that recent memories are stored in the hippocampus, while older memories are independent of the hippocampus and instead dependent on cortical areas. One problem with interpreting these studies is that memory for the contextual stimuli weakens as time passes between the training event and testing and older memories are often less detailed, making it difficult to determine if memory storage in the hippocampus is related to the age or to the accuracy of the memory. Activity of the mammalian target of rapamycin (mTOR) signaling pathway is known to be important for controlling protein translation necessary for both memory consolidation after initial learning and for the reconsolidation of memory after retrieval. We tested whether p70s6 kinase (p70s6K), a key component of the mTOR signaling pathway, is activated following retrieval of context fear memory in the dorsal hippocampus (DH) and anterior cingulate cortex (ACC) at 1, 10 or 36 days after context fear conditioning. We also tested whether strengthening memory for the contextual stimuli changed p70s6K phosphorylation in these structures 36 days after training. We show that under standard training conditions retrieval of a recently formed memory is initially precise and involves the DH. Over time it loses detail, becomes independent of the DH, and depends on the ACC. In a subsequent experiment we preserved the accuracy of older memories through pre-exposure to the training context. We show that remote memory still involved the DH in animals given pre-exposure. These data support the notion that detailed memories depend on the DH regardless of their age.
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