Feeding is regulated not solely by intrinsic energy demands, but also by various environmental cues. Food sight and odor are two essential food-related cues that promote human eating; nonetheless, the underlying neural mechanisms remain unknown. Here, we show that during energy deficit, food sight inhibits the ventromedial hypothalamus (VMH) neuronal activity, thereby promoting feeding and food-associated contextual memory in mice.
VMH neurons receive direct GABAergic input from the suprachiasmatic nucleus (SCN) that is rapidly activated by food sight. Either knockout of VMH RuvB-like 2 (RUVBL2) or inhibition of RUVBL2-expressing neurons in the VMH (VMHRUVBL2) promotes feeding and food-associated contextual memory. Interestingly, VMHRUVBL2 neurons exert these effects by sequentially projecting to the supramammillary nucleus (SuM) and the hippocampal dentate gyrus (DG).
Together, this study identifies SCNGABA → VMHRUVBL2 → SuM→DG neural circuit underlying food sight-promoted feeding and food-associated contextual memory in mice. Dandan Wang (Fudan University, Shanghai, China) and Fan Yang (Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, China) for sharing Ai14 and Sf1-Cre mouse models, respectively. Yong Xu (Baylor College of Medicine, USA) for constructive comments on this manuscript.
This work was supported by the National Natural Science Foundation of China (32571338, 31971076 and 32271202 to X.X., U23A20171 to W.J.Z., 32500848 to X.C.), the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2026ZD0556402 to W.J.Z.), the Natural Science Foundation of Liaoning Province (2025-MS-232 to Y.Z.), the China Postdoctoral Science Foundation (2025M782305 to Y.Z.), the Tianjin Municipal Science and Technology Commission (20JCJQJC00240 to X.X.), the National Key Research and Development Program of China (2019YFA0802500 to X.X. and W.J.Z.), the Scientific Research Funding of Tianjin Medical University Chu Hsien-I Memorial Hospital (ZXY-ZDSYSZD2025-2 to M.X.), the Brain Science and Brain-like Intelligence Technology-National Science and Technology Major Project, the neural circuit mechanisms of attention (2021ZD0203800 to S.Z.), the R&D Program of Guangzhou National Laboratory (GZNL2023A02012 to X.X. and W.J.Z.), and the Tianjin Key Medical Discipline Construction Project (TJYXZDXK-3-007B). These authors contributed equally: Juemou Zhou, Fumiao Zhang, Chen-Ma Wang. NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, The province and ministry co-sponsored collaborative innovation center for medical epigenetics, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China Juemou Zhou, Fumiao Zhang, Chen-Ma Wang, Ting Ouyang, Mingming Xing, Danting Ma, Chunguang Liu, Xiaofeng Shi, Bojie Hu, Weiping J.
Zhang & Xiangyang Xie Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology, Shenzhen, China State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang, China Department of Pathophysiology, Naval Medical University, Shanghai, China Correspondence to Yuqi Zhang, Weiping J. The authors declare that no competing interests exist. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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