Spatial organization and sex differences of paraventricular hypothalamic oxytocin neurons projecting to distinct brain regions.

Hypothalamic oxytocin (OXT) neurons play crucial roles in modulating various behaviors, including reward, feeding, and affective behaviors, via targeting downstream projections. Although the whole-brain projections of the paraventricular nucleus (PVN) OXT neurons have been dissected, the spatial distribution and sex differences of subpopulations targeting distinct regions remain poorly investigated. Here, utilizing retrograde tracing in mice, we mapped PVN oxytocin neurons projecting to the nucleus accumbens (NAc), lateral septum (LS), central amygdala (CeA), ventral tegmental area (VTA), and dorsal vagal complex (DVC). We found that OXT neurons projecting to these regions are predominantly located in the posterior PVN, and exhibit sex differences. Within the male group, DVC-projecting OXT neurons are the most abundant population, while within the female group, VTA- and DVC-projecting neurons show the highest cell number. Subregional analysis revealed that NAc-projecting neurons and DVC-projecting neurons in males distribute more ventrally, but VTA-projecting OXT neurons distribute more laterally compared to females. Comparing the spatial distributions of neurons projecting to different regions, in males, PVN-CeA neurons are more dorsal, while PVN-NAc groups are distributed more ventrally. In females, PVN-VTA neurons are distributed more laterally. These findings describe the spatial organization of PVN OXT neurons targeting distinct regions, providing a framework for future exploration of transcriptional, electrophysiological, circuitry, and functional properties of hypothalamic OXT neurons.