Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron. 2024 Oct 9;112(19):3354-3370.e5. doi: 10.1016/j.neuron.2024.07.017. Epub 2024 Aug 16.
The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin-receptor-expressing neurons in the dorsomedial hypothalamus (DMH) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.
食物的美味对于激励动物进食至关重要，但味觉是否在促进进食停止方面具有类似的功能还不是很清楚。在这里，我们发现与食物味道相关的信号会在每次摄食期间迅速抑制促进饥饿的 AgRP 神经元。通过闭环光遗传刺激阻断这些短暂的活动下降，选择性地延迟饱腹感的出现，从而增加食物摄入。我们发现，下丘脑背内侧核（DMH）中表达瘦素受体的上游神经元会对甜或脂肪味道做出反应，并在进食期间表现出与下游 AgRP 细胞同步的激活，这种激活模式是相反的。这些发现揭示了味觉在摄食负反馈控制中的意外作用。它们还揭示了一种机制，即 AgRP 神经元作为驱动饥饿的主要细胞，能够影响食物消耗的即时动态。
