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

Autores
Singh, Sudhuman; Wilson, Torri D.; Valdivia Torres, Lesly Spring; Benowitz, Barbara; Chaudhry, Sarah; Ma, Jun; Adke, Anisha P.; Soler Cedeño, Omar; Velasquez, Daniela; Penzo, Mario A.; Carrasquillo, Yarimar
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 hyper-sensitivity. 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.
Fil: Singh, Sudhuman. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Wilson, Torri D.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Valdivia Torres, Lesly Spring. National Center For Complementary And Integrative Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benowitz, Barbara. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Chaudhry, Sarah. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Ma, Jun. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Adke, Anisha P.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Soler Cedeño, Omar. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Velasquez, Daniela. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Penzo, Mario A.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Carrasquillo, Yarimar. National Center For Complementary And Integrative Health; Estados Unidos
Materia
PAIN
CIRCUIT
AMYGDALA
ZONA INCERTA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/publicdomain/zero/1.0/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/212796
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/212796
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in miceSingh, SudhumanWilson, Torri D.Valdivia Torres, Lesly SpringBenowitz, BarbaraChaudhry, SarahMa, JunAdke, Anisha P.Soler Cedeño, OmarVelasquez, DanielaPenzo, Mario A.Carrasquillo, YarimarPAINCIRCUITAMYGDALAZONA INCERTAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Central 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 hyper-sensitivity. 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.Fil: Singh, Sudhuman. National Center For Complementary And Integrative Health; Estados UnidosFil: Wilson, Torri D.. National Center For Complementary And Integrative Health; Estados UnidosFil: Valdivia Torres, Lesly Spring. National Center For Complementary And Integrative Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Benowitz, Barbara. National Center For Complementary And Integrative Health; Estados UnidosFil: Chaudhry, Sarah. National Center For Complementary And Integrative Health; Estados UnidosFil: Ma, Jun. National Center For Complementary And Integrative Health; Estados UnidosFil: Adke, Anisha P.. National Center For Complementary And Integrative Health; Estados UnidosFil: Soler Cedeño, Omar. National Center For Complementary And Integrative Health; Estados UnidosFil: Velasquez, Daniela. National Center For Complementary And Integrative Health; Estados UnidosFil: Penzo, Mario A.. National Center For Complementary And Integrative Health; Estados UnidosFil: Carrasquillo, Yarimar. National Center For Complementary And Integrative Health; Estados UnidoseLife Sciences Publications Ltd2022-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212796Singh, Sudhuman; Wilson, Torri D.; Valdivia Torres, Lesly Spring; Benowitz, Barbara; Chaudhry, Sarah; et al.; An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice; eLife Sciences Publications Ltd; eLife; 11; e68760; 10-2022; 1-312050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.68760info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/68760info:eu-repo/semantics/openAccesshttps://creativecommons.org/publicdomain/zero/1.0/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:55:45Zoai:ri.conicet.gov.ar:11336/212796instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:55:45.216CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 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
spellingShingle An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
Singh, Sudhuman
PAIN
CIRCUIT
AMYGDALA
ZONA INCERTA
title_short 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_sort An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice
dc.creator.none.fl_str_mv Singh, Sudhuman
Wilson, Torri D.
Valdivia Torres, Lesly Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P.
Soler Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A.
Carrasquillo, Yarimar
author Singh, Sudhuman
author_facet Singh, Sudhuman
Wilson, Torri D.
Valdivia Torres, Lesly Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P.
Soler Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A.
Carrasquillo, Yarimar
author_role author
author2 Wilson, Torri D.
Valdivia Torres, Lesly Spring
Benowitz, Barbara
Chaudhry, Sarah
Ma, Jun
Adke, Anisha P.
Soler Cedeño, Omar
Velasquez, Daniela
Penzo, Mario A.
Carrasquillo, Yarimar
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PAIN
CIRCUIT
AMYGDALA
ZONA INCERTA
topic PAIN
CIRCUIT
AMYGDALA
ZONA INCERTA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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 hyper-sensitivity. 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.
Fil: Singh, Sudhuman. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Wilson, Torri D.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Valdivia Torres, Lesly Spring. National Center For Complementary And Integrative Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Benowitz, Barbara. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Chaudhry, Sarah. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Ma, Jun. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Adke, Anisha P.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Soler Cedeño, Omar. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Velasquez, Daniela. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Penzo, Mario A.. National Center For Complementary And Integrative Health; Estados Unidos
Fil: Carrasquillo, Yarimar. National Center For Complementary And Integrative Health; Estados Unidos
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 hyper-sensitivity. 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.
publishDate 2022
dc.date.none.fl_str_mv 2022-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/212796
Singh, Sudhuman; Wilson, Torri D.; Valdivia Torres, Lesly Spring; Benowitz, Barbara; Chaudhry, Sarah; et al.; An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice; eLife Sciences Publications Ltd; eLife; 11; e68760; 10-2022; 1-31
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212796
identifier_str_mv Singh, Sudhuman; Wilson, Torri D.; Valdivia Torres, Lesly Spring; Benowitz, Barbara; Chaudhry, Sarah; et al.; An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice; eLife Sciences Publications Ltd; eLife; 11; e68760; 10-2022; 1-31
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.68760
info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/68760
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/publicdomain/zero/1.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/publicdomain/zero/1.0/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications Ltd
publisher.none.fl_str_mv eLife Sciences Publications Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782261413806080
score 12.982451

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