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 (...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2022 |
| Country: | España |
| Institution: | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| Repository: | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| OAI Identifier: | oai:i3pt.fundanetsuite.com:p1618 |
| Online Access: | 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: | Open access |
| Keyword: | 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) |
| _version_ | 1878740279049060352 |
|---|---|
| author | Velasco, ER |
| 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 |
| author_browse | Andero, R Das, P Flores, A Florido, A Garcia-Esteve, LL Gomez-Gomez, A Jovanovic, T Lori, A Newman, EL Norrholm, S Pozo, OJ Ressler, KJ Roca, A Ross, RA Senabre, E Torres, A 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 |
| collection | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d039b9d269fa01acaf6aa5dcfffdb9ca |
| institution | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| instname_str | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:i3pt.fundanetsuite.com:p1618 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | NATURE PORTFOLIO |
| publisherStr | NATURE PORTFOLIO |
| reponame_str | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| spelling | PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus 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 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) 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 PORTFOLIO 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 |
| 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) |
| status_str | publishedVersion |
| title | 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_short | PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus |
| title_sort | PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus |
| 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) |
| topic_facet | 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) |
| 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 |