Department of Bioengineering, Stanford University, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Nature. 2020 Nov;587(7834):437-442. doi: 10.1038/s41586-020-2905-5. Epub 2020 Nov 11.
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. Here 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. 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 genes associated with membrane fusion 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.
学习和短期记忆过程中的基因表达作用已经得到了广泛研究，但关于可以持续一生的远程记忆，人们知之甚少。在这里，我们使用长期的情境恐惧记忆作为范例，来探测内侧前额叶皮层中支持远程记忆存储的单细胞基因表达图谱。我们发现，在恐惧学习后数周内，不同神经元群体中存在持续的、与活动特异性相关的转录变化。在广泛的可塑性编码空间中，我们确定了与膜融合相关的基因，这些基因可能在远程记忆的维持中发挥重要作用。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了记忆回路。与远程记忆印痕相关的基因表达程序的发现，为现有的大脑分类图谱增加了一个重要的、与活动相关的细胞状态维度，并揭示了远程记忆存储的难以捉摸的机制。
