Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake
Ventral tegmental area GABAergic neurons induce anxiety-like behaviors and promote palatable food intake
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腹侧被盖区 GABA 能神经元诱发焦虑样行为并促进可口食物摄入
DOI：
10.1016/j.neuropharm.2020.108114
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发表时间：
2020-08-15
影响因子：
4.7
通讯作者：
Yu, Chang-Xi
中科院分区：
文献类型：
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作者：
Chen, Li;Lu, Yi-Ping;Yu, Chang-Xi
肥胖症的流行是一个全球性的问题，也是对公共卫生的巨大挑战。过度食用食物，特别是可口的食物，是肥胖的主要原因。食物过度消费背后的精确神经回路仍不清楚，需要进一步表征。在本研究中，我们发现，在腹侧被盖区（VTA）内的GABA能神经元的Ca~（2+）信号增加后的食物摄入开始，特别是高脂或高糖食物。腹侧被盖区GABA能神经元的光遗传学激活引起了立即进食可口的食物，并显着增加了饱食小鼠的可口食物摄入量。腹侧被盖区GABA能神经元的光抑制抑制可口食物的摄入。令人惊讶的是，腹侧被盖区GABA能神经元的光活化抑制了禁食小鼠对标准食物的摄入，但没有减少进食标准食物的持续时间。此外，我们还发现这些神经元的光激活在旷场、高架十字迷宫和大理石埋藏实验中引起了一系列的焦虑样行为。此外，我们还发现腹侧被盖区GABA能神经元向外侧下丘脑发出丰富的投射，外侧下丘脑中GABA能VTA末梢的光激活诱导了美味食物的过度消费，但不诱导焦虑样行为。综上所述，我们的研究结果表明，GABA能腹侧被盖区神经元是神经回路中的关键节点，这些神经回路是焦虑样行为和美味食物的过度喂养的基础，并且GABA能腹侧被盖区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。
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 over-consumption remain unclear and require further characterization. In the present study, we showed that Ca2+ 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.