Florido Torres, Antonio LuisVelasco, Eric R.Soto-Faguás, Carlos M.Gómez-Gómez, ÀlexPérez-Caballero, LauraMolina, PatriciaNadal, RoserPozo Mendoza, Óscar J., 1975-Saura, Carlos A.Andero, Raül2021-10-262021-10-262021Florido A, Velasco ER, Soto-Faguás CM, Gomez-Gomez A, Perez-Caballero L, Molina P, Nadal R, Pozo OJ, Saura CA, Andero R. Sex differences in fear memory consolidation via Tac2 signaling in mice. Nat Commun. 2021;12(1):2496. DOI: 10.1038/s41467-021-22911-92041-1723http://hdl.handle.net/10230/48808Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3β/β-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.application/pdfeng© The Author(s) 2021. 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/.Sex differences in fear memory consolidation via Tac2 signaling in miceinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-021-22911-9AmygdalaClassical conditioningFear conditioningPreclinical researchinfo:eu-repo/semantics/openAccess