MERFISH data for mouse brain with fear condition

<b>Spatial and single-cell transcriptomics reveal neuron-astrocyte interplay in long-term memory</b>Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala (BLA) is a center of salience networks that underlie emotional experiences and thus plays a key role in long-term fear memory formation. 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 brain-derived neurotrophic factor (BDNF) signaling, mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB) activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Strikingly, upon long-term memory formation a neuronal sub-population defined by increased <i>Penk</i> and decreased <i>Tac</i> expression constituted the most prominent component of the BLA’s memory engram. These transcriptional changes were observed both with single-cell RNAseq 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 further discover that this neuronal subpopulation interacts with adjacent astrocytes, and functional experiments then showed that neurons require interactions with astrocytes to encode long-term memory.Single cell RNAseq data is available at GSE246147