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

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 neu...

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Autores principales: Singh, Sudhuman, Wilson, Torri D, Valdivia, Spring, Benowitz, Barbara, Chaudhry, Sarah, Ma, Jun, Adke, Anisha P, Soler-Cedeño, Omar, Velasquez, Daniela, Penzo, Mario A, Carrasquillo, Yarimar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635874/
https://www.ncbi.nlm.nih.gov/pubmed/36269044
http://dx.doi.org/10.7554/eLife.68760
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author Singh, Sudhuman
Wilson, Torri D
Valdivia, Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P
Soler-Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A
Carrasquillo, Yarimar
author_facet Singh, Sudhuman
Wilson, Torri D
Valdivia, Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P
Soler-Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A
Carrasquillo, Yarimar
author_sort Singh, Sudhuman
collection PubMed
description 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.
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spelling pubmed-96358742022-11-05 An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice Singh, Sudhuman Wilson, Torri D Valdivia, Spring Benowitz, Barbara Chaudhry, Sarah Ma, Jun Adke, Anisha P Soler-Cedeño, Omar Velasquez, Daniela Penzo, Mario A Carrasquillo, Yarimar eLife Neuroscience 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. eLife Sciences Publications, Ltd 2022-10-21 /pmc/articles/PMC9635874/ /pubmed/36269044 http://dx.doi.org/10.7554/eLife.68760 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Neuroscience
Singh, Sudhuman
Wilson, Torri D
Valdivia, Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P
Soler-Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A
Carrasquillo, Yarimar
An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title_full An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title_fullStr An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title_full_unstemmed An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title_short An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
title_sort inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635874/
https://www.ncbi.nlm.nih.gov/pubmed/36269044
http://dx.doi.org/10.7554/eLife.68760
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