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Publication : Incerta-thalamic Circuit Controls Nocifensive Behavior via Cannabinoid Type 1 Receptors.

First Author  Wang H Year  2020
Journal  Neuron Volume  107
Issue  3 Pages  538-551.e7
PubMed ID  32502461 Mgi Jnum  J:292714
Mgi Id  MGI:6449294 Doi  10.1016/j.neuron.2020.04.027
Citation  Wang H, et al. (2020) Incerta-thalamic Circuit Controls Nocifensive Behavior via Cannabinoid Type 1 Receptors. Neuron 107(3):538-551.e7
abstractText  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 (CB1Rs) 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.
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