1. Incerta-thalamic Circuit Controls Nocifensive Behavior via Cannabinoid Type 1 Receptors.
- Author
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Wang H, Dong P, He C, Feng XY, Huang Y, Yang WW, Gao HJ, Shen XF, Lin S, Cao SX, Lian H, Chen J, Yan M, and Li XM
- Subjects
- Animals, Behavior, Animal, Endocannabinoids, Mice, Neural Inhibition, Neural Pathways, Neurons metabolism, Pain metabolism, Parvalbumins, Posterior Thalamic Nuclei cytology, Receptor, Cannabinoid, CB1 agonists, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Zona Incerta cytology, Neurons physiology, Nociception physiology, Pain physiopathology, Posterior Thalamic Nuclei physiology, Receptor, Cannabinoid, CB1 metabolism, Zona Incerta physiology
- Abstract
Pain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized. Here, we found that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting nocifensive behaviors, whereas selectively inhibiting ZIv-Po activity reduces nocifensive withdrawal responses. Furthermore, cannabinoid type 1 receptors (CB
1 Rs) are expressed specifically at ZIv-Po axon terminals in this circuit, and cannabinoids attenuate nocifensive responses through presynaptic inhibition. Selective inhibition of the ZIv-Po circuit or administration of cannabinoids into the Po are sufficient to ameliorate pathological pain. These findings identify the critical role of the ZIv-Po circuit and its modulation by endocannabinoids in controlling nocifensive behaviors., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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