DNA methyltransferase activity is required for memory-related neural plasticity in the lateral amygdala.

DNA methyltransferase activity is required for memory-related neural plasticity in the lateral amygdala.
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DOI:
10.1016/j.nlm.2013.11.008
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发表时间:
2014-01
影响因子:
2.7
通讯作者:
Schafe, Glenn E.
Schafe, Glenn E.
中科院分区:
心理学4区
文献类型:
--
作者:
Maddox, Stephanie A.;Watts, Casey S.;Schafe, Glenn E.

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我们先前已经证明,听觉巴甫洛夫恐惧条件反射与杏仁外侧核(LA)DNA甲基转移酶(DNMT)表达的增加有关,在体外,LA内灌流或沐浴DNMT活性抑制剂会损害听觉恐惧记忆和丘脑和皮质传入LA的长时程增强(LTP)的巩固。在本研究中,我们使用觉醒行为神经生理学技术,在活体内检测DNMT活性在伴随恐惧记忆巩固和再巩固的记忆相关神经生理学变化中的作用。我们发现,听觉恐惧条件作用导致LA中短潜伏期听觉诱发电位(AEFP)的幅度与训练相关的增强。LA内注射DNMT抑制剂会损害恐惧记忆的巩固,同时损害LA中与训练相关的神经可塑性的巩固;即LA中的短期记忆(STM)和训练相关的AEFP幅度的短期增加是完整的,而长期记忆(LTM)和训练相关的AEFP幅度增加的长期保持受到损害。在单独的实验中,我们发现,在听觉恐惧记忆提取后,LA内注入DNMT抑制剂对提取后STM或训练相关的LA中AEFP幅度变化的短期保留没有影响,但显著损害提取后LTM和LA中AEFP幅度变化的长期保留。这些发现首次证明了DNMT活性在体内记忆相关神经可塑性的巩固和再巩固中的必要性。
We have previously shown that auditory Pavlovian fear conditioning is associated with an increase in DNA methyltransferase (DNMT) expression in the lateral amygdala (LA) and that intra-LA infusion or bath application of an inhibitor of DNMT activity impairs the consolidation of an auditory fear memory and long-term potentiation (LTP) at thalamic and cortical inputs to the LA, in vitro. In the present study, we use awake behaving neurophysiological techniques to examine the role of DNMT activity in memory-related neurophysiological changes accompanying fear memory consolidation and reconsolidation in the LA, in vivo. We show that auditory fear conditioning results in a training-related enhancement in the amplitude of short-latency auditory-evoked field potentials (AEFPs) in the LA. Intra-LA infusion of a DNMT inhibitor impairs both fear memory consolidation and, in parallel, the consolidation of training-related neural plasticity in the LA; that is, short-term memory (STM) and short-term training-related increases in AEFP amplitude in the LA are intact, while long-term memory (LTM) and long-term retention of training-related increases in AEFP amplitudes are impaired. In separate experiments, we show that intra-LA infusion of a DNMT inhibitor following retrieval of an auditory fear memory has no effect on post-retrieval STM or short-term retention of training-related changes in AEFP amplitude in the LA, but significantly impairs both post-retrieval LTM and long-term retention of AEFP amplitude changes in the LA. These findings are the first to demonstrate the necessity of DNMT activity in the consolidation and reconsolidation of memory-associated neural plasticity, in vivo.
DOI: 10.1101/lm.1027208
发表时间: 2008-10
期刊: Learning & memory (Cold Spring Harbor, N.Y.)
影响因子: --
作者:
Duvarci S;Nader K;LeDoux JE
通讯作者: LeDoux JE
皮质DNA甲基化保持遥远的记忆。
DOI: 10.1038/nn.2560
发表时间: 2010-06
影响因子: 25
作者:
Miller, Courtney A.;Gavin, Cristin F.;White, Jason A.;Parrish, R. Ryley;Honasoge, Avinash;Yancey, Christopher R.;Rivera, Ivonne M.;Rubio, Maria D.;Rumbaugh, Gavin;Sweatt, J. David
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DOI: 10.1038/nn.2514
发表时间: 2010-04
影响因子: 25
作者:
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通讯作者: Fan, Guoping
DOI: 10.1037/0735-7044.113.2.276
发表时间: 1999-04-01
影响因子: 1.9
作者:
Bailey, DJ;Kim, JJ;Helmstetter, FJ
通讯作者: Helmstetter, FJ
DOI: 10.1523/jneurosci.1786-08.2008
发表时间: 2008-10-15
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
作者:
Lubin FD;Roth TL;Sweatt JD
通讯作者: Sweatt JD