mTOR signaling in the hippocampus is necessary for memory formation
mTOR signaling in the hippocampus is necessary for memory formation
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DOI：
10.1016/j.nlm.2006.08.007
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Medina, Jorge H.
中科院分区：
文献类型：
--
作者：
Bekinschtein, Pedro;Katche, Cynthia;Medina, Jorge H.
人们普遍认为，长期记忆（LTM）的形成需要mRNA翻译，但对大脑中调节这一过程的细胞机制知之甚少。哺乳动物雷帕霉素靶蛋白（mTOR）是一种重要的转录调节因子。在这里，我们表明，在大鼠中，一次试验抑制性回避（IA）的LTM形成，一个依赖于校园的恐惧动机的学习任务，需要mTOR激活。IA训练与mTOR及其底物核糖体S6激酶（p70S6K）磷酸化状态的快速增加特别相关。训练前15分钟（但不是训练后立即）双侧CA1内输注雷帕霉素（一种选择性mTOR抑制剂）完全阻碍IA LTM，而不影响短期记忆（STM）保持。因此，我们的研究结果表明，海马mRNA翻译的调节是记忆巩固的主要控制步骤。(c)2006年爱思唯尔公司All rights reserved.
It is widely accepted that the formation of long-term memory (LTM) requires mRNA translation, but little is known about the cellular mechanisms in the brain that regulate this process. Mammalian target of rapamycin (mTOR) is a key regulator of translational efficacy and capacity. Here, we show that LTM formation of one-trial inhibitory avoidance (IA) in rats, a hippocampus-dependent fear-motivated learning task, requires mTOR activation. IA training is specifically associated with a rapid increase in the phosphorylation state of mTOR and its substrate ribosomal S6 kinase (p70S6K). Bilateral intra-CA1 infusion of rapamycin, a selective mTOR inhibitor, 15 min before, but not immediately after training completely hinders IA LTM without affecting short-term memory (STM) retention. Therefore, our findings indicate that the regulation of hippocampal mRNA translation is a major control step in memory consolidation. (c) 2006 Elsevier Inc. All rights reserved.