Spatially resolved transcriptome profiling of the mouse prefrontal cortex in health and chronic pain

The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion, executive action to even pain processing. To decode the cellular and circuit organization of such diverse functions, we employed spatially resolved single-cell transcriptome profiling of PFC. Results revealed that PFC has distinct cell type composition and gene expression patterns relative to neighboring cortical areas - with neuronal excitability-regulating genes differently expressed. These cellular and molecular features further segregated within PFC subregions, alluding to the subregion-specificity of several PFC functions. PFC projects to major subcortical targets through combinations of neuronal subtypes, showing a target-intrinsic fashion. Finally, based on these features, we identified distinct cell types and circuits in PFC underlying chronic pain, an increasing healthcare challenge with limited molecular understanding. Collectively, this comprehensive map will facilitate understanding of discrete molecular, cellular and circuit mechanisms underlying specific PFC functions in health and disease.