Aitken Tara J, Ly Truong, Shehata Sarah, Sivakumar Nilla, Medina Naymalis La Santa, Gray Lindsay A, Dundar Naz, Barnes Chris, Knight Zachary A
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.
bioRxiv. 2023 Dec 3:2023.11.30.569492. doi: 10.1101/2023.11.30.569492.
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 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.
食物的诱人味道对于促使动物进食至关重要，但味道在促进进食终止方面是否具有类似功能，目前还不太清楚。我们在此表明，促进饥饿的AgRP神经元在每次进食期间会被与食物味道相关的信号迅速抑制。通过闭环光遗传学刺激阻断这些活动的短暂下降，可通过选择性延迟饱腹感的出现来增加食物摄入量。我们发现，下丘脑背内侧（DMH）中表达瘦素受体的上游神经元会对甜味或脂肪味做出反应，并在进食期间表现出与下游AgRP细胞相反的时间锁定激活。这些发现揭示了味道在进食负反馈控制中的意外作用。它们还揭示了一种机制，即驱动饥饿的主要细胞AgRP神经元能够影响食物消耗的即时动态。
