MicroRNA-182 regulates amygdala-dependent memory formation.
MicroRNA-182 regulates amygdala-dependent memory formation.
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DOI：
10.1523/jneurosci.2873-12.2013
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发表时间：
2013-01-23
期刊：
影响因子：
--
通讯作者：
Miller CA
中科院分区：
文献类型：
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作者：
Griggs EM;Young EJ;Rumbaugh G;Miller CA
从头蛋白质合成支持持久的功能和结构可塑性，是新记忆形成的分子要求。最近的证据表明，microRNA可能参与调节神经可塑性的分子机制。MicroRNA是内源性的非编码RNA，能够转录后抑制其mRNA靶点。为了探索microRNA介导的杏仁核依赖性记忆形成的调节潜力，我们在听觉恐惧条件反射后1小时对大鼠外侧杏仁核中的microRNA进行了表达谱分析。微阵列分析显示，超过一半的已知microRNA在外侧杏仁核中内源性表达，其中7种microRNA在听觉恐惧训练中上调，32种下调。生物信息学分析确定了几种下调的microRNA作为已知参与可塑性和记忆的肌动蛋白调节蛋白的潜在阻遏物。通过定量实时PCR证实了听觉恐惧条件反射对这些microRNA之一miR-182的下调。侧杏仁核内miR-182的过表达导致蛋白质的表达降低，而不是已知调节结构可塑性的两种突触富集的肌动蛋白调节因子corneum和Rac 1的mRNA。miR-182的过度表达也破坏了长期的听觉恐惧记忆，但不是短期的。这些数据表明，学习诱导的miR-182（一种以前在大脑中未被表征的microRNA）的抑制支持杏仁核中的长期记忆形成，并表明它至少部分地通过关键肌动蛋白调节蛋白的去抑制来实现。这些发现进一步表明，microRNA可能代表了一种以前未被充分认识的机制，用于调节记忆巩固过程中的蛋白质合成。
De novo protein synthesis supports long-lasting functional and structural plasticity and is a molecular requirement for new memory formation. Recent evidence has suggested that microRNAs may be involved in regulating the molecular mechanisms underlying neural plasticity. MicroRNAs are endogenous, non-coding RNAs capable of post-transcriptional repression of their mRNA targets. To explore the potential for microRNA-mediated regulation of amygdala-dependent memory formation, we performed expression profiling of microRNAs in the lateral amygdala of rats 1 hour after auditory fear conditioning. Microarray analysis revealed that over half of all known microRNAs are endogenously expressed in the lateral amygdala, with 7 microRNAs upregulated and 32 downregulated by auditory fear training. Bioinformatic analysis identified several of the downregulated microRNAs as potential repressors of actin-regulating proteins known to be involved in plasticity and memory. Downregulation of one of these microRNAs by auditory fear conditioning, miR-182, was confirmed by quantitative real-time PCR. Overexpression of miR-182 within the lateral amygdala resulted in decreased expression of the protein, but not mRNA of two synapse-enriched regulators of actin known to modulate structural plasticity, cortactin and Rac1. The overexpression of miR-182 also disrupted long-term, but not short-term auditory fear memory. These data indicate that learning-induced suppression of miR-182, a microRNA previously uncharacterized in the brain, supports long-term memory formation in the amygdala and suggests it does so, at least in part, through the derepression of key actin-regulating proteins. These findings further indicate that microRNAs may represent a previously underappreciated mechanism for regulating protein synthesis during memory consolidation.