@article{c809826f77624995bf8ac18638ef18c6,
title = "PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus",
abstract = "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.",
author = "Velasco, {E. R.} and A. Florido and Flores and E. Senabre and A. Gomez-Gomez and A. Torres and A. Roca and S. Norrholm and Newman, {E. L.} and P. Das and Ross, {R. A.} and A. Lori and Pozo, {O. J.} and Ressler, {K. J.} and Garcia-Esteve, {L. L.} and T. Jovanovic and R. Andero",
note = "Funding Information: We thank Drs. Javier Carrasco, N{\'u}ria Barba, Mar Castillo, Roser Nadal, Antonio Armario, Laura Perez-Caballero and Ignacio Mar{\'i}n Blasco at the Institute of Neurosciences, UAB. RA was supported by a NARSAD Young Investigator Grant #22434, Ram{\'o}n 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 Fundaci{\'o}n 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. {\'A}.F. was supported by FJCI-2016-29888 contract from MICINN. L.L.G.E. was a recipient of a grant from the Women{\textquoteright}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. Funding Information: We thank Drs. Javier Carrasco, N{\'u}ria Barba, Mar Castillo, Roser Nadal, Antonio Armario, Laura Perez-Caballero and Ignacio Mar{\'i}n Blasco at the Institute of Neurosciences, UAB. RA was supported by a NARSAD Young Investigator Grant #22434, Ram{\'o}n 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 Fundaci{\'o}n 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. {\'A}.F. was supported by FJCI-2016-29888 contract from MICINN. L.L.G.E. was a recipient of a grant from the Women{\textquoteright}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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-31442-w",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}