Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits

Autores
García, Ana Paula; Aitta Aho, Teemu; Schaaf, Laura; Heeley, Nicholas; Heuschmid, Lena; Bai, Yunjing; Barrantes, Francisco Jose; Apergis Schoute, John
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine's (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the α4 subunit. We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with di-hydros-ßerythroidine (DHβE), an α4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR α4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DHβE-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DHβE (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.
Fil: García, Ana Paula. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. University of Cambridge; Reino Unido
Fil: Aitta Aho, Teemu. University of Cambridge; Reino Unido
Fil: Schaaf, Laura. University of Cambridge; Reino Unido
Fil: Heeley, Nicholas. University of Cambridge; Reino Unido
Fil: Heuschmid, Lena. University of Cambridge; Reino Unido
Fil: Bai, Yunjing. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; España. University of Cambridge; Reino Unido. Institute Of Psychology; China
Fil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Apergis Schoute, John. University of Cambridge; Reino Unido
Materia
ACETYLCHOLINE RECEPTOR
ALPHA-4 SUBUNIT
APPETITE
HYPOTHALAMUS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182748
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/182748
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuitsGarcía, Ana PaulaAitta Aho, TeemuSchaaf, LauraHeeley, NicholasHeuschmid, LenaBai, YunjingBarrantes, Francisco JoseApergis Schoute, JohnACETYLCHOLINE RECEPTORALPHA-4 SUBUNITAPPETITEHYPOTHALAMUShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine's (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the α4 subunit. We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with di-hydros-ßerythroidine (DHβE), an α4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR α4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DHβE-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DHβE (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.Fil: García, Ana Paula. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. University of Cambridge; Reino UnidoFil: Aitta Aho, Teemu. University of Cambridge; Reino UnidoFil: Schaaf, Laura. University of Cambridge; Reino UnidoFil: Heeley, Nicholas. University of Cambridge; Reino UnidoFil: Heuschmid, Lena. University of Cambridge; Reino UnidoFil: Bai, Yunjing. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; España. University of Cambridge; Reino Unido. Institute Of Psychology; ChinaFil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Apergis Schoute, John. University of Cambridge; Reino UnidoPublic Library of Science2015-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182748García, Ana Paula; Aitta Aho, Teemu; Schaaf, Laura; Heeley, Nicholas; Heuschmid, Lena; et al.; Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits; Public Library of Science; Plos One; 10; 8; 8-2015; 1-171932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0133327info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133327info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:48Zoai:ri.conicet.gov.ar:11336/182748instacron: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:34982025-09-03 09:53:49.081CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
title Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
spellingShingle Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
García, Ana Paula
ACETYLCHOLINE RECEPTOR
ALPHA-4 SUBUNIT
APPETITE
HYPOTHALAMUS
title_short Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
title_full Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
title_fullStr Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
title_full_unstemmed Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
title_sort Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits
dc.creator.none.fl_str_mv García, Ana Paula
Aitta Aho, Teemu
Schaaf, Laura
Heeley, Nicholas
Heuschmid, Lena
Bai, Yunjing
Barrantes, Francisco Jose
Apergis Schoute, John
author García, Ana Paula
author_facet García, Ana Paula
Aitta Aho, Teemu
Schaaf, Laura
Heeley, Nicholas
Heuschmid, Lena
Bai, Yunjing
Barrantes, Francisco Jose
Apergis Schoute, John
author_role author
author2 Aitta Aho, Teemu
Schaaf, Laura
Heeley, Nicholas
Heuschmid, Lena
Bai, Yunjing
Barrantes, Francisco Jose
Apergis Schoute, John
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACETYLCHOLINE RECEPTOR
ALPHA-4 SUBUNIT
APPETITE
HYPOTHALAMUS
topic ACETYLCHOLINE RECEPTOR
ALPHA-4 SUBUNIT
APPETITE
HYPOTHALAMUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine's (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the α4 subunit. We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with di-hydros-ßerythroidine (DHβE), an α4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR α4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DHβE-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DHβE (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.
Fil: García, Ana Paula. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. University of Cambridge; Reino Unido
Fil: Aitta Aho, Teemu. University of Cambridge; Reino Unido
Fil: Schaaf, Laura. University of Cambridge; Reino Unido
Fil: Heeley, Nicholas. University of Cambridge; Reino Unido
Fil: Heuschmid, Lena. University of Cambridge; Reino Unido
Fil: Bai, Yunjing. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; España. University of Cambridge; Reino Unido. Institute Of Psychology; China
Fil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Apergis Schoute, John. University of Cambridge; Reino Unido
description Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine's (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the α4 subunit. We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with di-hydros-ßerythroidine (DHβE), an α4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR α4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DHβE-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DHβE (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.
publishDate 2015
dc.date.none.fl_str_mv 2015-08
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/11336/182748
García, Ana Paula; Aitta Aho, Teemu; Schaaf, Laura; Heeley, Nicholas; Heuschmid, Lena; et al.; Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits; Public Library of Science; Plos One; 10; 8; 8-2015; 1-17
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182748
identifier_str_mv García, Ana Paula; Aitta Aho, Teemu; Schaaf, Laura; Heeley, Nicholas; Heuschmid, Lena; et al.; Nicotinic α4 receptor-mediated cholinergic influences on food intake and activity patterns in hypothalamic circuits; Public Library of Science; Plos One; 10; 8; 8-2015; 1-17
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0133327
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133327
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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score 13.13397

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