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 (...
| Autores: | , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/55663 |
| Acceso en línea: | http://hdl.handle.net/10230/55663 http://dx.doi.org/10.1038/s41467-022-31442-w |
| Access Level: | acceso abierto |
| Palabra clave: | Fear conditioning Neuroscience |
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PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamusVelasco, Eric R.Florido Torres, Antonio LuisFlores de los Heros, África, 1985-Senabre, EricGómez-Gómez, ÀlexTorres, AntoniRoca, AntoniNorrholm, SethNewman, Emily L.Das, PayelRoss, Rachel A.Lori, A.Pozo Mendoza, Óscar J., 1975-Ressler, Kerry J.Garcia-Esteve, LluïsaJovanovic, TanjaAndero, RaülFear conditioningNeuroscienceExposure 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/ΔFosB 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.We thank Drs. Javier Carrasco, Núria Barba, Mar Castillo, Roser Nadal, Antonio Armario, Laura Perez-Caballero and Ignacio Marín Blasco at the Institute of Neurosciences, UAB. RA was supported by a NARSAD Young Investigator Grant #22434, Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R FEDER funds and PID2020-112705RB-I00 FEDER funds, ERANET-Neuron JTC 2019 ISCIII AC19/00077 and Fundación Koplowitz. A.F. received the predoctoral fellowship 2018 FI_B00030 from Generalitat de Catalunya. E.R.V. was supported by the BES-2017-080870 FPI-2017 fellowship from MINECO. Á.F. was supported by FJCI-2016-29888 contract from MICINN. L.L.G.E. was a recipient of a grant from the Women’s Institute of Spain (235/09). O.P. was supported by the Spanish Health National System CPII16/00027. K.J.R. and E.L.N. were supported by NIH P50 MH115874. E.L.N. was supported by NIH F32MH125634. R.A.R. and P.D. are supported by NIH K08 DK118201. S.N. received funding from VA Merit and Department of Defense.Nature Research202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55663http://dx.doi.org/10.1038/s41467-022-31442-wreponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Commun. 2022 Jul 28;13(1):4374info:eu-repo/grantAgreement/ES/1PE/RYC2014-15784info:eu-repo/grantAgreement/ES/1PE/SAF2016-76565-Rinfo:eu-repo/grantAgreement/ES/2PE/PID2020-112705RB-I00© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/556632026-05-29T05:05:01Z |
| 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, Eric R. Fear conditioning Neuroscience |
| 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, Eric R. Florido Torres, Antonio Luis Flores de los Heros, África, 1985- Senabre, Eric Gómez-Gómez, Àlex Torres, Antoni Roca, Antoni Norrholm, Seth Newman, Emily L. Das, Payel Ross, Rachel A. Lori, A. Pozo Mendoza, Óscar J., 1975- Ressler, Kerry J. Garcia-Esteve, Lluïsa Jovanovic, Tanja Andero, Raül |
| author |
Velasco, Eric R. |
| author_facet |
Velasco, Eric R. Florido Torres, Antonio Luis Flores de los Heros, África, 1985- Senabre, Eric Gómez-Gómez, Àlex Torres, Antoni Roca, Antoni Norrholm, Seth Newman, Emily L. Das, Payel Ross, Rachel A. Lori, A. Pozo Mendoza, Óscar J., 1975- Ressler, Kerry J. Garcia-Esteve, Lluïsa Jovanovic, Tanja Andero, Raül |
| author_role |
author |
| author2 |
Florido Torres, Antonio Luis Flores de los Heros, África, 1985- Senabre, Eric Gómez-Gómez, Àlex Torres, Antoni Roca, Antoni Norrholm, Seth Newman, Emily L. Das, Payel Ross, Rachel A. Lori, A. Pozo Mendoza, Óscar J., 1975- Ressler, Kerry J. Garcia-Esteve, Lluïsa Jovanovic, Tanja Andero, Raül |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Fear conditioning Neuroscience |
| topic |
Fear conditioning Neuroscience |
| 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/ΔFosB 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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10230/55663 http://dx.doi.org/10.1038/s41467-022-31442-w |
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http://hdl.handle.net/10230/55663 http://dx.doi.org/10.1038/s41467-022-31442-w |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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Nat Commun. 2022 Jul 28;13(1):4374 info:eu-repo/grantAgreement/ES/1PE/RYC2014-15784 info:eu-repo/grantAgreement/ES/1PE/SAF2016-76565-R info:eu-repo/grantAgreement/ES/2PE/PID2020-112705RB-I00 |
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http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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Nature Research |
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Nature Research |
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