Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain

The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and 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 the adult mouse 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 are 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, which emerge in a target-intrinsic fashion. Finally, based on these features, we identified distinct cell types and circuits in PFC underlying chronic pain, an escalating healthcare challenge with limited molecular understanding. Collectively, this comprehensive map will facilitate decoding of discrete molecular, cellular and circuit mechanisms underlying specific PFC functions in health and disease. Spatial transcriptomics reveals distinct composition and organization of cells and circuits in the mouse prefrontal cortex (PFC) relative to adjacent cortices, which concur with PFC's diverse functions, and also help detect neurons involved in chronic pain.

Automated summary

The prefrontal cortex (PFC) shows distinct cellular and molecular features, as well as circuit organization, which are associated with its diverse functions. This study provides insights into the specific mechanisms underlying PFC functions, including chronic pain.