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 pro...

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Bibliographic Details
Published in:Nature neuroscience 2023-11, Vol.26 (11), p.1880-1893
Main Authors: Bhattacherjee, Aritra, Zhang, Chao, Watson, Brianna R., Djekidel, Mohamed Nadhir, Moffitt, Jeffrey R., Zhang, Yi
Format: Article
Language:English
Subjects:
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Animal Genetics and Genomics
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Chronic pain
Circuits
Cognition
Composition
Decoding
Excitability
Gene expression
Neurobiology
Neurosciences
Pain
Prefrontal cortex
Transcriptomes
Transcriptomics
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Summary: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.
ISSN:1097-6256
1546-1726
DOI:10.1038/s41593-023-01455-9