美国斯坦福大学Stephen R. Quake等研究人员合作发现，空间转录组学揭示神经元-星形胶质细胞在长期记忆中的协同作用。2024年2月7日，《自然》杂志在线发表了这项成果。

研究人员利用空间和单细胞转录组学阐明了杏仁基底外侧在长期记忆中的细胞和分子结构。研究人员在神经元和星形胶质细胞亚群中发现了转录特征，这些特征具有记忆特异性并可持续数周。这些转录特征表明，神经肽和BDNF信号、MAPK和CREB激活、泛素化途径以及突触连接是长期记忆的关键组成部分。值得注意的是，在长期记忆形成时，由Penk表达增加和Tac表达减少所定义的神经元亚群构成了杏仁核基底外侧记忆印记的最主要组成部分。

通过单细胞RNA测序和完整切片中的单分子空间转录组学研究，研究人员观察到了这些转录变化，从而为记忆刻痕提供了丰富的空间图谱。空间数据使研究人员能够确定这一神经元亚群与邻近的星形胶质细胞相互作用，功能实验表明神经元需要与星形胶质细胞相互作用才能编码长期记忆。

据介绍，记忆对过去的经历进行编码，从而使未来的计划成为可能。杏仁基底外侧是支撑情绪体验的显著性网络的中心，因此在长期恐惧记忆的形成中起着关键作用。

附：英文原文

Title: Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory

Author: Sun, Wenfei, Liu, Zhihui, Jiang, Xian, Chen, Michelle B., Dong, Hua, Liu, Jonathan, Sdhof, Thomas C., Quake, Stephen R.

Issue&Volume: 2024-02-07

Abstract: Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has a key role in long-term fear memory formation1. Here we used spatial and single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and BDNF signalling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Notably, upon long-term memory formation, a neuronal subpopulation defined by increased Penk and decreased Tac expression constituted the most prominent component of the memory engram of the basolateral amygdala. These transcriptional changes were observed both with single-cell RNA sequencing and with single-molecule spatial transcriptomics in intact slices, thereby providing a rich spatial map of a memory engram. The spatial data enabled us to determine that this neuronal subpopulation interacts with adjacent astrocytes, and functional experiments show that neurons require interactions with astrocytes to encode long-term memory.

DOI: 10.1038/s41586-023-07011-6

Source: https://www.nature.com/articles/s41586-023-07011-6