2. Academic Validation
  3. A bottom-up septal inhibitory circuit mediates anticipatory control of drinking

A bottom-up septal inhibitory circuit mediates anticipatory control of drinking

  • Nat Neurosci. 2025 Sep 22. doi: 10.1038/s41593-025-02056-4.
Lingyu Xu # 1,  Yuhao Sun # 2,  Chenyuan Huang # 3,  Yanrong Zheng # 1,  Jialu Chen 2,  Xiaolong Ma 1,  Qiujie Shi 1,  Mengting Liu 1,  Xiaoyun Qiu 1,  Qikun Zhao 2,  Chenshu Gao 1,  Jie Liao 2,  Yi Wang 1 2,  Zhong Chen 4 5
Affiliations

Affiliations

  • 1 Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
  • 2 Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
  • 3 Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 4 Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. chenzhong@zju.edu.cn.
  • 5 Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. chenzhong@zju.edu.cn.
  • # Contributed equally.
PMID: 40983715 DOI: 10.1038/s41593-025-02056-4
Abstract

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 SFOCaMKII 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.

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