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dmPFC-vlPAG projection neurons contribute to pain maintenance
RV virus was injected for cell-type-specific retrograde trans-synaptic tracing, hChR2-EYFP and hChR2-mCherry viruses were injected for optogenetic experiments, hM4D-EGFP virus was injected for the chemogenetic test. (all viruses were packaged by BrainVTA)
The viruses used in this article from BrainVTA are in the table below
RV  R01002 RV-ENVA-ΔG-DsRed
Tracing Helper  PT-0062 AAV2/9-DIO- EGFP-TVA
 PT-0023 rAAV2/9-Ef1α-DIO-RVG
CRE Recombinase  PT-0136 AAV2/2Retro-hSyn-Cre
 sCAAV2/1-hSyn-FLEX-EGFP
Optogenetic  PT-0296 AAV2/2-CaMKlla- hChR2-EYFP、
 PT-0366 AAV/2/9-mDlx-hChR2-mCherry 
Chemogenetics  AAV2/9-hSyn-DIO-hM4D-EGFP
Control  PT-0107 AAV2/2-CaMKIIα-EYFP
Pub Date: 2019-11-03, DOI: 10.1172/JCI127607  Email: [email protected]
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
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.
Fig.1 Using multiple tracing methods to dissect the dmPFC-vlPAG neural pathway.
In order to investigate the projection of dmPFC to vlPAG, the researchers used a variety of morphology and trans-synaptic virus tracing methods (From BrainVTA) to reveal two downward pain-regulating neural pathways. Finally, a dmPFC-vlPAG neural pathway was shown that it might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors. which provided a new target and scientific experimental basis for establishing an effective analgesic strategy.
 
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