LAUSR

Significance The neuropeptide system encompasses the most diverse family of neurotransmitters, but their expression, cellular localization, and functional role in the human brain have received limited attention. Here, we study human postmortem samples from prefrontal cortex (PFC), a key brain region, and employ RNA sequencing and RNAscope methods integrated with published single-cell data. Our aim is to characterize the distribution of peptides and their receptors in 17 PFC subregions and to explore their role in chemical signaling. The results suggest that the well-established anatomical and functional heterogeneity of human PFC is also reflected in the expression pattern of the neuropeptides. Our findings support ongoing efforts from academia and pharmaceutical companies to explore the potential of neuropeptide receptors as targets for drug development.