Oxytocin (OT) and vasopressin (VP) are evolutionarily conserved neuropeptides that regulate social behavior, emotional processing and physiological homeostasis. Although traditionally studied as individual modulators of affiliation, stress and autonomic function, emerging evidence indicates that their actions are best understood at the level of neural circuits. Advances in optogenetics, cell-type-specific electrophysiology and systems neuroscience have revealed that OT and VP act within distributed networks through receptor-defined microcircuits composed of excitatory and inhibitory neuronal populations, astrocytes and long-range projections. Within these circuits, OT and VP can exert complementary, synergistic or opposing effects depending on receptor localization, cellular identity and network state. Here, we synthesize recent circuit-level and electrophysiological evidence to propose a framework in which OT and VP operate as a coordinated neuromodulatory axis. We argue that the functional consequences of OT/VP signaling emerge not from peptide identity alone, but from their engagement of recurrent circuit motifs that redistribute excitation and inhibition across neural networks. These motifs provide a mechanistic substrate for regulating transitions between competing behavioral and physiological states, including social safety vs. threat, affiliation vs. avoidance, and parasympathetic vs. sympathetic dominance. We further discuss how disruption of receptor topology, synaptic integration and circuit architecture may contribute to neurodevelopmental, psychiatric and stress-related disorders. By shifting the focus from peptide-centric models to circuit-level mechanisms, this framework reconciles seemingly contradictory findings across brain regions and behavioral paradigms, and provides a foundation for the development of next-generation circuit-based therapeutic strategies targeting the oxytocin-vasopressin axis.
Radically different