An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice.

Autor:	Singh S; National Center for Complementary and Integrative Health, Bethesda, United States., Wilson TD; National Center for Complementary and Integrative Health, Bethesda, United States., Valdivia S; National Center for Complementary and Integrative Health, Bethesda, United States., Benowitz B; National Center for Complementary and Integrative Health, Bethesda, United States., Chaudhry S; National Center for Complementary and Integrative Health, Bethesda, United States., Ma J; National Institute of Mental Health, Bethesda, United States., Adke AP; National Center for Complementary and Integrative Health, Bethesda, United States., Soler-Cedeño O; National Center for Complementary and Integrative Health, Bethesda, United States., Velasquez D; National Center for Complementary and Integrative Health, Bethesda, United States., Penzo MA; National Institute of Mental Health, Bethesda, United States., Carrasquillo Y; National Center for Complementary and Integrative Health, Bethesda, United States.; National Institutes on Drug Abuse, National Institutes of Health, Bethesda, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Oct 21; Vol. 11. Date of Electronic Publication: 2022 Oct 21.
DOI:	10.7554/eLife.68760
Abstrakt:	Central amygdala neurons expressing protein kinase C-delta (CeA-PKCδ) are sensitized following nerve injury and promote pain-related responses in mice. The neural circuits underlying modulation of pain-related behaviors by CeA-PKCδ neurons, however, remain unknown. In this study, we identified a neural circuit that originates in CeA-PKCδ neurons and terminates in the ventral region of the zona incerta (ZI), a subthalamic structure previously linked to pain processing. Behavioral experiments show that chemogenetic inhibition of GABAergic ZI neurons induced bilateral hypersensitivity in uninjured mice and contralateral hypersensitivity after nerve injury. In contrast, chemogenetic activation of GABAergic ZI neurons reversed nerve injury-induced hypersensitivity. Optogenetic manipulations of CeA-PKCδ axonal terminals in the ZI further showed that inhibition of this pathway reduces nerve injury-induced hypersensitivity whereas activation of the pathway produces hypersensitivity in the uninjured paws. Altogether, our results identify a novel nociceptive inhibitory efferent pathway from CeA-PKCδ neurons to the ZI that bidirectionally modulates pain-related behaviors in mice. Competing Interests: SS, TW, SV, BB, SC, JM, AA, OS, DV, MP, YC No competing interests declared
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu