RXFP1-positive interface islands is a key piece of evidence in favor of the NUDAP hypothesis. This selective OPRM1 enrichment suggests the intriguing possibility that NUDAPs are part of the network of “hedonic hotspots?” Hedonic hotspots are regions in the NAc and ventral pallidum that, when opioids are directly applied, produce behavioral reactions that indicate pleasure.51 As might be expected for hedonic hotspots, the κ-opioid receptor gene (OPRK1) was absent from D1-NUDAP cells (Figure S7D). These differentially expressed genes and others provide a blueprint for understanding cell-type-specific contributions of this novel cell type to reward processing and pleasure.
