Xu Lingyu, Sun Yuhao, Huang Chenyuan, Zheng Yanrong, Chen Jialu, Ma Xiaolong, Shi Qiujie, Liu Mengting, Qiu Xiaoyun, Zhao Qikun, Gao Chenshu, Liao Jie, Wang Yi, Chen Zhong
Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Nat Neurosci. 2025 Sep 22. doi: 10.1038/s41593-025-02056-4.
Drinking behavior is not only homeostatically regulated but also rapidly adjusted before any changes in blood osmolality occur, known as anticipatory thirst satiation. Homeostatic and anticipatory signals converge in the subfornical organ (SFO); however, the neural pathways conveying peripheral information to the SFO before changes in blood composition are incompletely understood. Here we reveal an inhibitory pathway from the medial septum (MS) to the SFO that is involved in the control of anticipatory drinking behavior in mice. MS γ-aminobutyric acid (GABA)ergic neurons encode water-satiation signals by integrating cues from the oral cavity and tracking gastrointestinal signals. These neurons receive inputs from the parabrachial nucleus and relay to SFO neurons, forming a bottom-up pathway with activity that prevents overhydration. Disruption of this circuit leads to excessive water intake and hyponatremia. Our findings reveal a septal pathway that integrates multiple layers of presystemic signals to fine-tune drinking behavior.
饮水行为不仅受到稳态调节，而且在血液渗透压发生任何变化之前就会迅速调整，这被称为预期性口渴饱足。稳态信号和预期信号在穹窿下器官（SFO）汇聚；然而，在血液成分变化之前将外周信息传递到SFO的神经通路尚未完全明确。在这里，我们揭示了一条从小内侧隔核（MS）到SFO的抑制性通路，该通路参与了对小鼠预期饮水行为的控制。MSγ-氨基丁酸（GABA）能神经元通过整合来自口腔的线索并追踪胃肠道信号来编码水饱足信号。这些神经元接收来自臂旁核的输入并传递给SFO神经元，形成一条自下而上的通路，其活动可防止水分摄入过多。该回路的破坏会导致水分摄入过多和低钠血症。我们的研究结果揭示了一条隔区通路，该通路整合了多层系统前信号以微调饮水行为。
