Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fujian, 350108, China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fujian, 350108, China.
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fujian, 350108, China.
Neuropharmacology. 2020 Aug 15;173:108114. doi: 10.1016/j.neuropharm.2020.108114. Epub 2020 May 4.
The obesity epidemic is a global problem and a great challenge for public health. Overconsumption of food, especially palatable food, is the leading cause of obesity. The precise neural circuits underlying food overconsumption remain unclear and require further characterization. In the present study, we showed that Ca signals of GABAergic neurons within the ventral tegmental area (VTA) increased after the onset of food intake, especially high-fat or high-sugar chow. Optogenetic activation of VTA GABAergic neurons evoked immediate eating of palatable food and significantly increased palatable food intake in satiated mice. Photoinhibition of VTA GABAergic neurons suppressed palatable food intake. Surprisingly, photoactivation of VTA GABAergic neurons suppressed the intake of standard chow in fasted mice, but did not reduce the duration of eating of standard chow. Moreover, we found that photoactivation of these neurons drove a series of anxiety-like behaviors in the open field, elevated plus maze, and marble-burying test. Additionally, we found that VTA GABAergic neurons sent abundant projections to the lateral hypothalamus and photoactivation of GABAergic VTA terminals in the lateral hypothalamus induced overconsumption of palatable food, but not anxiety-like behaviors. Taken together, our results illustrate that GABAergic VTA neurons are a key node in the neural circuitry underlying anxiety-like behavior and over-feeding of palatable food, and that over-excitation of GABAergic VTA neurons may underlie clinical diseases related to anxiety and obesity.
肥胖症是一个全球性的问题，也是公共卫生的一大挑战。食物摄入过多，尤其是美味食物的摄入过多，是导致肥胖的主要原因。导致食物摄入过多的确切神经回路仍不清楚，需要进一步研究。在本研究中，我们发现，腹侧被盖区（VTA）中 GABA 能神经元的钙信号在进食开始后增加，尤其是高脂肪或高糖食物。VTA GABA 能神经元的光遗传学激活会立即引起对美味食物的进食，并显著增加饱食小鼠对美味食物的摄入量。VTA GABA 能神经元的光抑制抑制了美味食物的摄入。令人惊讶的是，VTA GABA 能神经元的光激活抑制了禁食小鼠对标准食物的摄入量，但并没有减少对标准食物的进食时间。此外，我们发现这些神经元的光激活在开阔场、高架十字迷宫和藏丸试验中引发了一系列类似焦虑的行为。此外，我们发现 VTA GABA 能神经元向外侧下丘脑发出丰富的投射，光激活外侧下丘脑的 GABA 能 VTA 末梢会导致美味食物的过度摄入，但不会引起类似焦虑的行为。总之，我们的研究结果表明，GABA 能 VTA 神经元是焦虑样行为和美味食物过度进食的神经回路中的一个关键节点，GABA 能 VTA 神经元的过度兴奋可能是与焦虑和肥胖相关的临床疾病的基础。
