The hypothalamo-neurohypophysial system (HNS), comprising hypothalamic magnocellular neuroendocrine cells (MNCs) and the neurohypophysis, plays a pivotal role in regulating reproduction and fluid homeostasis by releasing oxytocin and vasopressin into the bloodstream. However, its structure and contribution to the central actions of oxytocin and vasopressin remain incompletely understood. Using viral tracing and whole-brain imaging, we reconstruct the three-dimensional architecture of the HNS and observe collaterals of MNCs within the brain. By dual viral tracing, we further uncover that subsets of MNCs collaterally project to multiple extrahypothalamic regions. Selective activation of magnocellular oxytocin neurons promote peripheral oxytocin release and facilitate central oxytocin-mediated social interactions, whereas inhibition of these neurons elicit opposing effects. Our work reveals the previously unrecognized complexity of the HNS and provides structural and functional evidence for MNCs in coordinating both peripheral and central oxytocin-mediated actions, which will shed light on the mechanistic understanding of oxytocin-related psychiatric diseases.

下丘脑神经下垂系统（HNS）包括下丘脑大细胞神经内分泌细胞（MNC）和神经下垂体，通过将催产素和加压素释放到血液中来调节生殖和体液稳态。但是，其结构和对催产素和加压素的主要作用的贡献仍未完全了解。使用病毒追踪和全脑成像，我们重建了HNS的三维结构，并观察了大脑内MNC的侧支。通过双重病毒示踪，我们进一步发现，MNC的子集并发投射到多个下丘脑区域。大细胞催产素神经元的选择性激活促进外周催产素的释放并促进催产素介导的社交互动，而抑制这些神经元会引起相反的作用。我们的工作揭示了HNS以前无法识别的复杂性，并为跨国公司协调催产素介导的周围和中央作用提供了结构和功能证据，这将阐明对催产素相关精神疾病的机理理解。