Comparative atlas of PVN oxytocin and vasopressin systems reveals sex-conserved input–output wiring

Oxytocin and vasopressin are pleiotropic, structurally similar neuropeptides with well-established roles in the regulation of social behavior and homeostatic functions. Both neuropeptides support sexually dimorphic behaviors, ranging from lactation and uterine contractions for oxytocin to male-typical territorial aggression for vasopressin. Whether oxytocin and vasopressin circuits share similar input-output architecture has not been examined. Similarly, it remains unknown whether sex differences exist within the oxytocin and vasopressin central circuits. To close these gaps, we generated quantitative anterograde projection and retrograde input maps for the paraventricular hypothalamic oxytocin and vasopressin systems in mice. We observed that oxytocinergic and vasopressinergic neurons retain similar synaptic input architecture, with largely shared hypothalamic area inputs and some divergence across thalamic and pallidal afferents. In contrast, axonal projection patterns showed substantial differences between oxytocin and vasopressin neurons, with the former more densely innervating a broad range of forebrain and hindbrain regions. Comparisons across sex revealed no significant differences in synaptic inputs and outputs, for either the oxytocin or vasopressin systems. On average, brain regions that provided synaptic inputs to the paraventricular nucleus (PVN) oxytocin or vasopressin neurons tended to be balanced, in that they also received projection outputs from the respective brain area. Together, our data represent a comparative study of PVN oxytocin and vasopressin input-output architecture, highlighting a prominent recurrent organizational motif in both systems and their broadly sex-conserved organization at the macroscale level.