AAV-eArchT3.0 was used for photoinhibition tests. AAV-GCaMP6m was used for fiber photometry recordings. AAV- hChR2 was used for cell-selective photoactivation of VTA GABAergic neurons. (From
BrainVTA)
The viruses used in this article are in the table below
|
CRE Recombinase |
PT-0346 AAV-Vgat-Cre-WPRE-PA |
|
Optogenetic |
PT-0002 AAV-hEF1a-DIO-hChR2-mCherry-WPRE-PA
AAV-hSyn-DIO-eArchT3.0-EGFP |
|
Calcium sensors |
AAV-hSyn-DIO-GCaMP6m |
Li Chen, Yi-Ping Lu, Hui-Yun Chen, Sheng-Nan Huang, Yu-Rou Guo, Jing-Yuan Zhang, Qi-Xuan Li, Chen-Yu Luo, Shao-Wei Lin, Zhao-Nan Chen, Li-Huan Hu, Wen-Xiang Wang, Huang-Yuan Li, Ping Cai, Chang-Xi Yu
Pub Date: 2020-04-17,
DOI: 10.1016/j.neuropharm.2020.108114,
Email: [email protected]
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 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.
Figure 1. VTA GABAergic Neurons are Selectively Activated by Optogenetic Photostimulation.
This study is aimed to explore the precise neural circuits underlying food overconsumption. Using fiber photometry and optogenetic manipulation, the results clearly demonstrate that VTA GABAergic neurons play an important role in regulating anxiety-like behaviors and in promoting intake of palatable food.
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