The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control^1,2,3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a ‘bedside-to-bench’ approach for the identification of neural circuits that influence behaviour.

大脑是体重稳态的场所。然而，我们无法控制日益流行的肥胖症，这凸显了需要超越规范的喂养途径来扩大我们对体重控制的理解^1,2,3. 在这里，我们使用反向翻译方法来识别并从解剖学、分子和功能上表征促进饱食的神经集合。无偏见的、基于任务的功能性磁共振成像显示，患有以食欲不振为特征的遗传性疾病患者的小脑对食物的反应存在显着差异。小鼠的转录组学分析揭示了小脑前深核 (aDCN) 中在分子和地形学上不同的神经元，这些神经元被肠道中的进食或营养输注激活。aDCN 神经元的选择性激活通过减少进餐量而显着减少了食物摄入量，而没有代谢率的补偿性变化。我们发现 aDCN 活动通过增加纹状体多巴胺水平和减弱对后续食物消耗的阶段性多巴胺反应来终止食物摄入。我们的研究定义了一个保守的饱食中心，它可能代表了管理过度饮食的新治疗目标，并强调了“床边到工作台”方法在识别影响行为的神经回路方面的效用。