Institute for Systems Physiology, Faculty of Medicine, University of Cologne and University Clinic Cologne, Cologne 50931, Germany; Max Planck Institute for Metabolism Research, Cologne 50931, Germany.
Institute for Systems Physiology, Faculty of Medicine, University of Cologne and University Clinic Cologne, Cologne 50931, Germany; Max Planck Institute for Metabolism Research, Cologne 50931, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne 50931, Germany.
Cell Metab. 2023 Mar 7;35(3):456-471.e6. doi: 10.1016/j.cmet.2023.02.008. Epub 2023 Feb 23.
Animals continuously weigh hunger and thirst against competing needs, such as social contact and mating, according to state and opportunity. Yet neuronal mechanisms of sensing and ranking nutritional needs remain poorly understood. Here, combining calcium imaging in freely behaving mice, optogenetics, and chemogenetics, we show that two neuronal populations of the lateral hypothalamus (LH) guide increasingly hungry animals through behavioral choices between nutritional and social rewards. While increased food consumption was marked by increasing inhibition of a leptin receptor-expressing (LepR) subpopulation at a fast timescale, LepR neurons limited feeding or drinking and promoted social interaction despite hunger or thirst. Conversely, neurotensin-expressing LH neurons preferentially encoded water despite hunger pressure and promoted water seeking, while relegating social needs. Thus, hunger and thirst gate both LH populations in a complementary manner to enable the flexible fulfillment of multiple essential needs.
动物会根据自身状态和机会，持续权衡饥饿感和干渴感与其他需求（如社交和交配）的相对重要性。然而，感知和评估营养需求的神经元机制仍知之甚少。在这里，我们通过结合自由活动的小鼠钙成像、光遗传学和化学遗传学研究，发现下丘脑外侧核（LH）的两个神经元群体引导越来越饥饿的动物在营养和社交奖励之间做出行为选择。在快速时间尺度上，随着食物消耗的增加，瘦素受体表达（LepR）亚群的抑制作用增强，而 LepR 神经元会限制进食或饮水，并促进社交互动，即使在饥饿或口渴的情况下也是如此。相反，神经降压素表达的 LH 神经元优先编码水，尽管存在饥饿压力，但会促进水的寻找，而将社交需求放在次要位置。因此，饥饿和口渴以互补的方式调节 LH 神经元群体，从而实现多种基本需求的灵活满足。
