Department of Neurobiology and Department of Neurosurgery of Second Affiliated Hospital, Key Laboratory for Biomedical Engineering of Education Ministry, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University, Hangzhou, Zhejiang 310020, China.
Cell Rep. 2019 Jul 16;28(3):616-624.e5. doi: 10.1016/j.celrep.2019.06.051.
Overeating is a serious issue in modern society, causing many health problems, including obesity. Although the hypothalamus has been previously identified as the key brain structure that regulates body weight homeostasis, the downstream pathways and non-canonical neural circuitry involved in feeding behavior remain largely uncharacterized. Here, we discover that suppressing the activity of GABAergic cells in the anterior ventrolateral periaqueductal gray (vlPAG), whether directly or through long-projection GABAergic inputs from either the bed nucleus of the stria terminalis (BNST) or the lateral hypothalamus (LH), is sufficient to promptly induce feeding behavior in well-fed mice. In contrast, optogenetic activation of these cells interrupts food intake in starved mice. Long-term chemogenetic manipulation of vlPAG GABAergic cell activity elicits a corresponding change in mouse body weight. Our studies reveal distinct midbrain GABAergic pathways and highlight an important role of GABAergic cells in the anterior vlPAG in feeding behavior.
暴饮暴食是现代社会的一个严重问题，会导致许多健康问题，包括肥胖。尽管下丘脑先前已被确定为调节体重平衡的关键大脑结构，但涉及摄食行为的下游途径和非经典神经回路在很大程度上仍未被描述。在这里，我们发现，无论是直接抑制腹外侧导水管周围灰质（vlPAG）的 GABA 能细胞的活动，还是通过来自终纹床核（BNST）或外侧下丘脑（LH）的长投射 GABA 能输入来抑制其活动，都足以迅速诱导饱腹小鼠摄食行为。相比之下，光遗传激活这些细胞会中断饥饿小鼠的摄食。长期化学遗传操纵 vlPAG GABA 能细胞的活动会引起小鼠体重的相应变化。我们的研究揭示了中脑 GABA 能途径的差异，并强调了前 vlPAG 中的 GABA 能细胞在摄食行为中的重要作用。
