Uncovering the brain-wide pattern of synaptic input to vasopressin-expressing neurons in the paraventricular nucleus of the hypothalamus.

Arginine vasopressin (AVP) is a neuropeptide critical for the mammalian stress response and social behavior. AVP produced in the hypothalamus regulates water osmolality and vasoconstriction in the body, and in the brain, it regulates social behavior, aggression, and anxiety. However, the circuit mechanisms that link AVP to social behavior, homeostatic function, and disease are not well understood. This study investigates the circuit configurations of AVP-expressing neurons in the rodent hypothalamus and characterizes synaptic input from the entire brain. We targeted the paraventricular nucleus (PVN) using retrograde viral tracing techniques to identify direct afferent synaptic connections made onto AVP-expressing neurons. AVP neurons in the PVN display region-specific anatomical configurations that reflect their unique contributions to homeostatic function, motor behaviors, feeding, and affiliative behavior. The afferent connections identified were similar in both sexes and subsequent molecular investigation of these inputs shows that those local hypothalamic inputs are overwhelmingly nonpeptidergic cells indicating a potential interneuron nexus between hormone cell activation and broader cortical connection. This proposed work reveals new insights into the organization of social behavior circuits in the brain, and how neuropeptides act centrally to modulate social behaviors.