Sex differences in cell type-specific transcriptional programs and GPCR signaling in the human subgenual anterior cingulate cortex

Female-enriched CHRM2 expression in PVALB interneurons of the human sgACC predicts sex-specific M2 receptor effects on firing rates in mouse prefrontal cortex.

• Why it matters: Psychiatric traits differ by sex, but the molecular basis in non-psychiatric brains across distinct neuronal populations is unclear, limiting mechanistic links to treatment variation.
• What they did: RNA-seq from laser-capture microdissected sgACC neurons (10 males, 9 females) compared excitatory pyramidal and SST-, PVALB-, and VIP interneurons, then assessed GPCR transcript sex differences and tested M2 function with patch-clamp in mouse prefrontal cortex.
• The result: CHRM2 in PVALB cells showed the second strongest sex difference (female enrichment), and M2 activation increased maximal firing rates in PVALB cells from female but not male mice.

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