MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Cell Rep. 2017 Dec 19;21(12):3559-3572. doi: 10.1016/j.celrep.2017.11.089.
Feeding requires the integration of homeostatic drives with emotional states relevant to food procurement in potentially hostile environments. The ventromedial hypothalamus (VMH) regulates feeding and anxiety, but how these are controlled in a concerted manner remains unclear. Using pharmacogenetic, optogenetic, and calcium imaging approaches with a battery of behavioral assays, we demonstrate that VMH steroidogenic factor 1 (SF1) neurons constitute a nutritionally sensitive switch, modulating the competing motivations of feeding and avoidance of potentially dangerous environments. Acute alteration of SF1 neuronal activity alters food intake via changes in appetite and feeding-related behaviors, including locomotion, exploration, anxiety, and valence. In turn, intrinsic SF1 neuron activity is low during feeding and increases with both feeding termination and stress. Our findings identify SF1 neurons as a key part of the neurocircuitry that controls both feeding and related affective states, giving potential insights into the relationship between disordered eating and stress-associated psychological disorders in humans.
进食需要将与食物获取相关的稳态驱动力与潜在敌对环境中的情绪状态整合在一起。腹内侧下丘脑 (VMH) 调节进食和焦虑,但这些如何协同控制仍不清楚。我们使用药理学、光遗传学和钙成像方法以及一系列行为测定,证明 VMH 类固醇生成因子 1 (SF1) 神经元构成了一个营养敏感的开关,调节进食和避免潜在危险环境的竞争动机。SF1 神经元活性的急性改变会通过改变食欲和与进食相关的行为(包括运动、探索、焦虑和情绪)来改变食物摄入。反过来,进食期间 SF1 神经元的内在活性较低,并且随着进食的结束和压力的增加而增加。我们的发现将 SF1 神经元确定为控制进食和相关情感状态的神经回路的关键部分,为理解人类饮食失调与应激相关心理障碍之间的关系提供了潜在的见解。