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

Authors :
Sudhuman Singh
Torri D Wilson
Spring Valdivia
Barbara Benowitz
Sarah Chaudhry
Jun Ma
Anisha P Adke
Omar Soler-Cedeño
Daniela Velasquez
Mario A Penzo
Yarimar Carrasquillo
Source :
eLife, Vol 11 (2022)
Publication Year :
2022
Publisher :
eLife Sciences Publications Ltd, 2022.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.48b7a2adcce84354a70ebc688f5a5a42
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.68760