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dmPFC-vlPAG projection neurons contribute to pain threshold m
AAV-hChR2 was used for optogenetic manipulation. AAV- hM3Dq was used for chemogenetics manipulation. RV and viruses of tracing helper were for rabies-based transsynaptic tracing. (All the viruses were from BrainVTA)
The viruses used in this article from BrainVTA are in the table below
 Optogenetic  PT-0296 AAV2/2-CaMKIIα-hChR2-EYFP
 Chemogenetics  PT-0891 AAV2/9-hSyn-DIO-hM3Dq-eGFP-WPRE-pA
 Tracing Helper  PT-0062 AAV2/9-DIO-EGFP-TVA
 PT-0023 AAV2/9-DIO-RG
 CRE Recombinase  PT-0136 AAV2/2Retro-hSyn-Cre-WPRE-pA
 Control  PT-0107 AAV2/2-CaMKIIα-EYFP
 PT-1134 AAV2/9-mDlx-mCherry-WPRE-pA
 RV  RV-EnvA-ΔG-dsRed
Jun-Bin Yin, Shao-Hua Liang, Fei Li, Wen-Jun Zhao, Yang Bai, Yi Sun, Zhen-Yu Wu, Tan Ding, Yan Sun, Hai-Xia Liu, Ya-Cheng Lu, Ting Zhang, Jing Huang, Tao Chen, Hui Li, Zhou-Feng Chen, Jing Cao, Rui Ren, Ya-Nan Peng, Juan Yang, Wei-Dong Zang, Xiang Li, Yu-Lin Dong, Yun-Qing Li
Pub Date: 2020-08-25, DOI: 10.1172/jci127607, Email:
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 GABAA receptor (GABAAR) 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.

Figure 1. Projections from the dmPFC to the VGLUT2-containing neurons in the vlPAG.
This study is aimed to explore the role of the dorsal medial prefrontal cortex (dmPFC) in nociceptive modulation and the underlying neural pathway and the function of specific cell types. The authors applied chemical lesion, optogenetic, chemogenetic, molecular biological, and behavioral pharmacological approaches to demonstrate the involvement of the descending dmPFC/vlPAG pathway in pain modulation and negative emotion processing.
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