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The mechanisms through which immune activation might drive depressive symptoms remain elusive, limiting the ability to develop new targeted therapies. Using a mouse model of neuroinflammation, involving a TLR7\/8 agonist, we combined whole-brain and spatial transcriptomics approaches to determine whether TLR7\/8-driven neuroinflammation resulted in consistent immune and neurobiological transcriptional changes throughout the brain. We found evidence of strong immune activation throughout the brain,. and this global inflammatory signal led to regionally specific changes in gene expression. 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