Volume 41, Issue 7, July, 2025


Complexity of the Hypothalamic Oxytocin System and its Involvement in Brain Functions and Diseases

 Xiao Cui1  · Lei Xiao1
1 Shanghai Stomatological Hospital and School of Stomatology, The State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science and the Institutes of Brain Science, Fudan University, Shanghai 200032, China

Abstract
Oxytocin is classically termed a ‘prosocial neuropeptide’ because of its evolutionarily conserved role in promoting affiliative behaviors. Endogenous oxytocin is mainly synthesized by hypothalamic oxytocin neurons and signals through oxytocin receptors (OxtRs). Recent studies with cell type-specific and circuit-specific interrogation have uncovered that oxytocin signals exert pleiotropic neuromodulatory effects through anatomically widespread axonal projections and ubiquitously distributed OxtRs. Dysfunctions of oxytocin signals are closely relevant to brain disorders/diseases. While intranasal oxytocin administration has been demonstrated to be one potential strategy to alleviate some brain disorders/diseases, such as autism, obesity, and anxiety, conflicting clinical outcomes highlight the imperative for precision-targeted neuromodulation strategies. Dissecting the molecular, cellular, and neural circuitry mechanisms underlying oxytocinergic modulation is a prerequisite to achieving this goal. This review provides an overview of the current understanding of the oxytocin system in terms of anatomical structure, neuronal modulation, and signal pathways, and discusses the modulatory roles of oxytocin in social, feeding, emotional, and sensory-related brain functions and brain diseases.

Keywords
Oxytocin; Oxytocin neuron; Oxytocin receptor; Neural circuit; Brain disease; Diversity