PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (...

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Autores: Velasco, ER, Florido, A, Flores, A, Senabre, E, Gomez-Gomez, A, Torres, A, Roca, A, Norrholm, S, Newman, EL, Das, P, Ross, RA, Lori, A, Pozo, OJ, Ressler, KJ, Garcia-Esteve, LL, Jovanovic, T, Andero, R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:i3pt.fundanetsuite.com:p1618
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/1618
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135194989&doi=10.1038%2fs41467-022-31442-w&partnerID=40&md5=ec2f1d8fbea08a5558597bedf5963ab7
Access Level:acceso abierto
Palabra clave:Animals
Extinction, Psychological
Fear
Female
Humans
Hypothalamus
Mice
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
hypophysis adenylate cyclase activating polypeptide
hypophysis adenylate cyclase activating polypeptide receptor 1
brain
gene expression
genotype
polymorphism
protein
RNA
animal
fear
female
genetics
human
hypothalamus
metabolism
mouse
physiology
reinforcement (psychology)
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network_name_str España
repository_id_str
spelling PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamusVelasco, ERFlorido, AFlores, ASenabre, EGomez-Gomez, ATorres, ARoca, ANorrholm, SNewman, ELDas, PRoss, RALori, APozo, OJRessler, KJGarcia-Esteve, LLJovanovic, TAndero, RAnimalsExtinction, PsychologicalFearFemaleHumansHypothalamusMicePituitary Adenylate Cyclase-Activating PolypeptideReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type Ihypophysis adenylate cyclase activating polypeptidehypophysis adenylate cyclase activating polypeptide receptor 1braingene expressiongenotypepolymorphismproteinRNAanimalfearfemalegeneticshumanhypothalamusmetabolismmousephysiologyreinforcement (psychology)Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/Delta FosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction. The PACAP-PAC1R neuropeptide system regulates neuroendocrine stress responses. Here the authors demonstrate a role for PACAP-PAC1R in ventromedial hypothalamus in modulating fear extinction.NATURE PORTFOLIO2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/1618https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135194989&doi=10.1038%2fs41467-022-31442-w&partnerID=40&md5=ec2f1d8fbea08a5558597bedf5963ab7Nature CommunicationsISSN: 20411723reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:i3pt.fundanetsuite.com:p16182026-06-21T15:30:37Z
dc.title.none.fl_str_mv PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
spellingShingle PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
Velasco, ER
Animals
Extinction, Psychological
Fear
Female
Humans
Hypothalamus
Mice
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
hypophysis adenylate cyclase activating polypeptide
hypophysis adenylate cyclase activating polypeptide receptor 1
brain
gene expression
genotype
polymorphism
protein
RNA
animal
fear
female
genetics
human
hypothalamus
metabolism
mouse
physiology
reinforcement (psychology)
title_short PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_full PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_fullStr PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_full_unstemmed PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
title_sort PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus
dc.creator.none.fl_str_mv Velasco, ER
Florido, A
Flores, A
Senabre, E
Gomez-Gomez, A
Torres, A
Roca, A
Norrholm, S
Newman, EL
Das, P
Ross, RA
Lori, A
Pozo, OJ
Ressler, KJ
Garcia-Esteve, LL
Jovanovic, T
Andero, R
author Velasco, ER
author_facet Velasco, ER
Florido, A
Flores, A
Senabre, E
Gomez-Gomez, A
Torres, A
Roca, A
Norrholm, S
Newman, EL
Das, P
Ross, RA
Lori, A
Pozo, OJ
Ressler, KJ
Garcia-Esteve, LL
Jovanovic, T
Andero, R
author_role author
author2 Florido, A
Flores, A
Senabre, E
Gomez-Gomez, A
Torres, A
Roca, A
Norrholm, S
Newman, EL
Das, P
Ross, RA
Lori, A
Pozo, OJ
Ressler, KJ
Garcia-Esteve, LL
Jovanovic, T
Andero, R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Animals
Extinction, Psychological
Fear
Female
Humans
Hypothalamus
Mice
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
hypophysis adenylate cyclase activating polypeptide
hypophysis adenylate cyclase activating polypeptide receptor 1
brain
gene expression
genotype
polymorphism
protein
RNA
animal
fear
female
genetics
human
hypothalamus
metabolism
mouse
physiology
reinforcement (psychology)
topic Animals
Extinction, Psychological
Fear
Female
Humans
Hypothalamus
Mice
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
hypophysis adenylate cyclase activating polypeptide
hypophysis adenylate cyclase activating polypeptide receptor 1
brain
gene expression
genotype
polymorphism
protein
RNA
animal
fear
female
genetics
human
hypothalamus
metabolism
mouse
physiology
reinforcement (psychology)
description Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/Delta FosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction. The PACAP-PAC1R neuropeptide system regulates neuroendocrine stress responses. Here the authors demonstrate a role for PACAP-PAC1R in ventromedial hypothalamus in modulating fear extinction.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://i3pt.portalinvestigacion.com/publicaciones/1618
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135194989&doi=10.1038%2fs41467-022-31442-w&partnerID=40&md5=ec2f1d8fbea08a5558597bedf5963ab7
url https://i3pt.portalinvestigacion.com/publicaciones/1618
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135194989&doi=10.1038%2fs41467-022-31442-w&partnerID=40&md5=ec2f1d8fbea08a5558597bedf5963ab7
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv NATURE PORTFOLIO
publisher.none.fl_str_mv NATURE PORTFOLIO
dc.source.none.fl_str_mv Nature Communications
ISSN: 20411723
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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