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

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

14 March 2024 | Wenfei Sun1,2,6, Zhihui Liu2,3,6, Xian Jiang2, Michelle B. Chen1, Hua Dong4, Jonathan Liu5, Thomas C. Südhof2,3,6 & Stephen R. Quake1,5,6
Spatial transcriptomics reveals neuron–astrocyte synergy in long-term memory formation. The basolateral amygdala (BLA) plays a critical role in long-term fear memory. Using spatial and single-cell transcriptomics, researchers identified memory-specific transcriptional signatures in neurons and astrocytes that persist for weeks. These signatures involve neuropeptide and BDNF signaling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity. A neuronal subpopulation with increased *Penk* and decreased *Tac* expression (P^T^ neurons) constitutes the most prominent part of the memory engram in the BLA. These neurons interact with adjacent astrocytes, which are also involved in long-term memory consolidation. Spatial transcriptomics enabled the identification of astrocytes that undergo gene-expression changes during memory formation and are required for memory consolidation. The study also revealed that similar molecular programs and cell types are used in long-term fear memories across different brain regions. Astrocytes exhibit persistent gene-expression changes during memory recall, suggesting they are 'engram astrocytes'. The study further showed that the astrocyte engram gene *Igfbp2* is essential for long-term memory formation. These findings highlight the critical role of neuron–astrocyte interactions in long-term memory consolidation and suggest that neuropeptides, including neurotensin, are key agents in memory formation. The results provide a comprehensive understanding of the cellular and molecular mechanisms underlying long-term memory formation and consolidation.Spatial transcriptomics reveals neuron–astrocyte synergy in long-term memory formation. The basolateral amygdala (BLA) plays a critical role in long-term fear memory. Using spatial and single-cell transcriptomics, researchers identified memory-specific transcriptional signatures in neurons and astrocytes that persist for weeks. These signatures involve neuropeptide and BDNF signaling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity. A neuronal subpopulation with increased *Penk* and decreased *Tac* expression (P^T^ neurons) constitutes the most prominent part of the memory engram in the BLA. These neurons interact with adjacent astrocytes, which are also involved in long-term memory consolidation. Spatial transcriptomics enabled the identification of astrocytes that undergo gene-expression changes during memory formation and are required for memory consolidation. The study also revealed that similar molecular programs and cell types are used in long-term fear memories across different brain regions. Astrocytes exhibit persistent gene-expression changes during memory recall, suggesting they are 'engram astrocytes'. The study further showed that the astrocyte engram gene *Igfbp2* is essential for long-term memory formation. These findings highlight the critical role of neuron–astrocyte interactions in long-term memory consolidation and suggest that neuropeptides, including neurotensin, are key agents in memory formation. The results provide a comprehensive understanding of the cellular and molecular mechanisms underlying long-term memory formation and consolidation.
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