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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/212796
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T10:22:58Zoai: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:34982025-09-29 10:22:58.37CONICET 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 |
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1844614222896431104 |
score |
13.070432 |