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.

记忆对过去的经历进行编码，从而实现未来的计划。基底外侧杏仁核是情绪体验背后的显着网络中心，因此在长期恐惧记忆的形成中发挥着关键作用¹ 。在这里，我们使用空间和单细胞转录组学来阐明基底外侧杏仁核在长期记忆中的作用的细胞和分子结构。我们在神经元和星形胶质细胞亚群中发现了具有记忆特异性并持续数周的转录特征。这些转录特征表明神经肽和 BDNF 信号传导、MAPK 和 CREB ​​激活、泛素化途径和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表达减少定义的神经元亚群构成了基底外侧杏仁核记忆印迹的最重要组成部分。通过单细胞 RNA 测序和完整切片中的单分子空间转录组学观察到这些转录变化，从而提供了丰富的记忆印迹空间图。空间数据使我们能够确定该神经元亚群与邻近的星形胶质细胞相互作用，并且功能实验表明神经元需要与星形胶质细胞相互作用来编码长期记忆。