1. dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors
- Author
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Zhou-Feng Chen, Zhen-Yu Wu, Yun-Qing Li, Wen-Jun Zhao, Shao-Hua Liang, Xiang Li, Yu-Lin Dong, Ting Zhang, Hui Li, Rui Ren, Yan Sun, Ya-Cheng Lu, Juan Yang, Fei Li, Ya-Nan Peng, Tao Chen, Jing Huang, Yang Bai, Yi Sun, Hai-Xia Liu, Jing Cao, Wei-Dong Zang, Jun-Bin Yin, and Tan Ding
- Subjects
0301 basic medicine ,Prefrontal Cortex ,Mice, Transgenic ,Optogenetics ,Receptors, Metabotropic Glutamate ,Inhibitory postsynaptic potential ,Mice ,03 medical and health sciences ,Neural Pathway ,0302 clinical medicine ,Neural Pathways ,Threshold of pain ,Animals ,Medicine ,Prefrontal cortex ,business.industry ,GABAA receptor ,Chronic pain ,General Medicine ,medicine.disease ,030104 developmental biology ,Nociception ,Anti-Anxiety Agents ,030220 oncology & carcinogenesis ,Chronic Pain ,business ,Neuroscience ,Research Article - Abstract
The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABA(A) receptor (GABA(A)R) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.
- Published
- 2020