Spatial transcriptomics reveals neuron-astrocyte synergy in long-term memory. This study uses spatial and single-cell transcriptomics to investigate the cellular and molecular mechanisms underlying long-term memory formation in the basolateral amygdala (BLA). The research identifies memory-specific transcriptional signatures in neurons and astrocytes that persist for weeks, implicating neuropeptide and BDNF signaling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. A neuronal subpopulation with increased PenK and decreased Tac expression constitutes the most prominent part of the memory engram in the BLA. These transcriptional changes are observed in intact slices using single-cell RNA sequencing and single-molecule spatial transcriptomics, providing a spatial map of the memory engram. The spatial data show that these neurons interact with adjacent astrocytes, and functional experiments demonstrate that neurons require astrocyte interactions to encode long-term memory. The study also reveals that astrocytes undergo gene-expression changes during long-term memory formation and are required for memory consolidation. Integration of these results with previous data on long-term contextual fear memory in the medial prefrontal cortex shows that similar molecular programs and cell types are used in long-term fear memories across different brain regions. The study highlights the role of astrocyte remodelling and neuron-astrocyte interactions in memory consolidation, with astrocytes expressing genes like Igfbp2 that are essential for long-term memory formation. The findings suggest that engram cells and their associated astrocytes play a critical role in memory consolidation, with persistent gene-expression programs and interactions between neurons and astrocytes being essential for long-term memory formation.Spatial transcriptomics reveals neuron-astrocyte synergy in long-term memory. This study uses spatial and single-cell transcriptomics to investigate the cellular and molecular mechanisms underlying long-term memory formation in the basolateral amygdala (BLA). The research identifies memory-specific transcriptional signatures in neurons and astrocytes that persist for weeks, implicating neuropeptide and BDNF signaling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. A neuronal subpopulation with increased PenK and decreased Tac expression constitutes the most prominent part of the memory engram in the BLA. These transcriptional changes are observed in intact slices using single-cell RNA sequencing and single-molecule spatial transcriptomics, providing a spatial map of the memory engram. The spatial data show that these neurons interact with adjacent astrocytes, and functional experiments demonstrate that neurons require astrocyte interactions to encode long-term memory. The study also reveals that astrocytes undergo gene-expression changes during long-term memory formation and are required for memory consolidation. Integration of these results with previous data on long-term contextual fear memory in the medial prefrontal cortex shows that similar molecular programs and cell types are used in long-term fear memories across different brain regions. The study highlights the role of astrocyte remodelling and neuron-astrocyte interactions in memory consolidation, with astrocytes expressing genes like Igfbp2 that are essential for long-term memory formation. The findings suggest that engram cells and their associated astrocytes play a critical role in memory consolidation, with persistent gene-expression programs and interactions between neurons and astrocytes being essential for long-term memory formation.