Persistent transcriptional programmes are associated with remote memory.

Persistent transcriptional programmes are associated with remote memory.
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DOI:
10.1038/s41586-020-2905-5
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发表时间:
2020-11
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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基因表达在学习和短期记忆中的作用已被广泛研究,但对可能持续一生的远程记忆知之甚少。我们使用长期情境恐惧记忆作为范例来探索在内侧前额叶皮层中远程记忆存储的单细胞基因表达景观。值得注意的是,我们在不同的神经元群体中发现了持续活动特异性转录改变,这种改变在恐惧学习后持续了数周。在巨大的可塑性编码空间中,我们发现了可能在维持远程记忆中起重要作用的膜融合基因。出乎意料的是,星形胶质细胞和小胶质细胞也获得了与远程记忆相关的持久基因表达特征,这表明它们积极参与记忆回路。与远程记忆印迹相关的基因表达程序的发现为现有的脑分类图谱增加了活动依赖细胞状态的重要维度,并揭示了远程记忆存储的难以捉摸的机制。
The role of gene expression during learning and in short-term memories has been studied extensively, but less is known about remote memories, which can persist for a lifetime. We used long-term contextual fear memory as a paradigm to probe the single-cell gene expression landscape that underlies remote memory storage in the medial prefrontal cortex. Remarkably, we found persistent activity-specific transcriptional alterations in diverse populations of neurons that lasted for weeks after fear learning. Out of a vast plasticity-coding space, we identified membrane-fusion genes that could have important roles in the maintenance of remote memory. Unexpectedly, astrocytes and microglia also acquired persistent gene expression signatures that were associated with remote memory, suggesting that they actively contribute to memory circuits. The discovery of gene expression programmes associated with remote memory engrams adds an important dimension of activity-dependent cellular states to existing brain taxonomy atlases and sheds light on the elusive mechanisms of remote memory storage.
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