Brainwide input-output architecture of paraventricular oxytocin and vasopressin neurons

Summary Oxytocin and vasopressin are pleiotropic neuropeptides with well-established roles in the regulation of social behavior and homeostatic functions. Their structural similarity and conserved functions in vertebrate social behavior suggest that neurohypophyseal peptides may represent a single integrative neuromodulatory system, yet both peptides subserve sexually dimorphic functions at the behavioral level. The extent to which central oxytocin and vasopressin systems share similar circuit architecture has not been previously studied. Sex differences in the central circuitry of the oxytocin and vasopressin systems may underlie sex-variant behaviors, but it is currently unknown whether the synaptic inputs or outputs of each neuropeptidergic system vary across males and females. To close this gap, we generated quantitative anterograde and retrograde maps of the paraventricular oxytocin and vasopressin systems in mice. We observed that both oxytocinergic and vasopressinergic neurons share highly similar synaptic inputs that are sex-conserved. Projection patterns differed across systems and showed sex differences, more pronounced in the vasopressin neurons. Together our data represent the first comparative study of oxytocin and vasopressin input-output architecture highlighting how these neurohypopheseal peptides can play complementary and overlapping roles that are sex-dependent.