Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Affiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong University of Science and Technology, 430012, Wuhan, China.
Mol Psychiatry. 2020 May;25(5):1006-1021. doi: 10.1038/s41380-019-0506-1. Epub 2019 Sep 5.
Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMC neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DA neurons). We further revealed that POMC neurons project to the VTA and provide an inhibitory tone to DA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMC→VTA circuit in mice increases body weight and food intake, and reduces depression-like behaviors and anhedonia in mice exposed to chronic restraint stress. Thus, our results identified a novel neurocircuitry regulating feeding and mood in response to stress.
慢性应激会导致情绪和能量稳态失调，但这些改变的神经回路仍有待充分阐明。在这里，我们证明了慢性束缚应激会导致小鼠下丘脑弓状核中前阿黑皮素原神经元（POMC 神经元）的过度活跃，同时伴随着腹侧被盖区多巴胺神经元（DA 神经元）的神经活动减少。我们进一步揭示了 POMC 神经元投射到 VTA，并通过直接和间接的神经传递对 DA 神经元施加抑制性影响。最后，我们发现抑制小鼠的 POMC→VTA 回路可增加体重和食物摄入量，并减少慢性束缚应激小鼠的抑郁样行为和快感缺失。因此，我们的研究结果确定了一个新的神经回路，该回路可调节应激反应中的摄食和情绪。
