The role of NR4A transcription factors in memory formation.

The role of NR4A transcription factors in memory formation.
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DOI:
10.1016/j.brainresbull.2011.02.001
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发表时间:
2011-04-25
影响因子:
3.8
通讯作者:
Abel T
Abel T
中科院分区:
医学3区
文献类型:
--
作者:
Hawk JD;Abel T

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在各种生理环境中,Nr 4a基因作为立即早期反应的一部分响应于外部刺激而转录,所述立即早期反应启动基因表达的级联反应,最终在这些环境中的每一个中导致不同的生理结果。在大多数情况下,启动Nr 4a基因表达的信号通路由升高的细胞内cAMP激活PKA组成,这反过来又导致CREB磷酸化和新基因合成。该cAMP-PKA-CREB通路是形成长期记忆的中心分子通路。事实上,学习诱导Nr 4a家族基因表达,长期记忆的形成需要学习后至少两波转录,这表明NR 4A核受体可能有助于第二波基因表达。在这篇文章中,我们回顾了在其他生理背景下获得的关于Nr 4a功能和调节的见解,并强调了这些经验教训如何应用于记忆形成的研究。
In various physiological contexts, Nr4a genes are transcribed in response to external stimuli as part of an immediate early response that initiates a cascade of gene expression ultimately leading to distinct physiological outcomes in each of these contexts. The signaling pathway that initiates Nr4a gene expression in most of these contexts consists of elevated intracellular cAMP activating PKA, which in turn leads to phosphorylation of CREB and new gene synthesis. This cAMP-PKA-CREB pathway is a central molecular pathway in the formation of a long-term memory. Indeed, learning induces Nr4a family gene expression, and long-term memory formation requires at least two waves of transcription after learning, suggesting that NR4A nuclear receptors may contribute to the second of these waves of gene expression. In this article, we review insights gained in other physiological contexts regarding Nr4a function and regulation and highlight how these lessons can be applied to the study of memory formation.
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