TY - JOUR
T1 - Sex differences in fear memory consolidation via Tac2 signaling in mice
AU - Florido, A.
AU - Velasco, E. R.
AU - Soto-Faguás, C. M.
AU - Gomez-Gomez, A.
AU - Perez-Caballero, L.
AU - Molina, P.
AU - Nadal, R.
AU - Pozo, O. J.
AU - Saura, C. A.
AU - Andero, R.
N1 - Funding Information:
The authors thank Mar Castillo, Dr. Javier Carrasco, and Núria Barba, technicians at the Institute of Neuroscience, UAB. We especially thank Dr. Antonio Armario for their valuable contribution to commenting on the manuscript as a member of the excellence 2017 SGR-00457 group (Generalitat de Catalunya). We thank Nicole Gouws for her help with the graphic design. We thank Gleb Shumyatsky for help with IPA and Cristina Márquez for help with CTT. We would also like to thank Noemí Haro for help with estradiol determination. Procedural images were created with BioRender.com. RA was supported by a NARSAD Young Investigator Grant #22434, Ramón y Cajal program RYC2014-15784, RETOS-MICINN SAF2016-76565-R FEDER funds, and ERANET-Neuron JTC 2019 ISCIII AC19/00077. CAS is supported by Ministerio de Ciencia e Inovación (MICINN) grant SAF2016-80027-R, PID2019-106615RB-100, and ISCIII (CIBERNED CB06/05/0042). RN was supported by MICINNgrant SAF2017-83430 and was a recipient of an ICREA Academia Award (Generalitat de Catalunya, 2015-2019). AF 2018 FI_B00030 and CMS 2017 FI_B00326 were recipients of Generalitat de Catalunya predoctoral fellowship. ERV was supported by BES-2017-080870 FPI-2017 fellowship from MINECO. LPC was supported by an FJC2018-037958-I (MCIyU). PM received support from FPU16/05416 (MCECD). OP was supported by the Spanish Health National System CPII16/00027.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Memory 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/GSK3 beta/beta -Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory. The Tachykinin 2 (Tac2) pathway in the central amygdala is sufficient and necessary for modulating fear memory consolidation. The authors show that silencing Tac2 neurons in the amygdala of male mice reduces fear expression, while fear expression in female mice is increased when manipulations are made during proestrus.
AB - Memory 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/GSK3 beta/beta -Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory. The Tachykinin 2 (Tac2) pathway in the central amygdala is sufficient and necessary for modulating fear memory consolidation. The authors show that silencing Tac2 neurons in the amygdala of male mice reduces fear expression, while fear expression in female mice is increased when manipulations are made during proestrus.
UR - http://www.scopus.com/inward/record.url?scp=85105163425&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/831ec62a-122b-39f2-af0a-935c08300e98/
U2 - https://doi.org/10.1038/s41467-021-22911-9
DO - https://doi.org/10.1038/s41467-021-22911-9
M3 - Article
C2 - 33941789
AN - SCOPUS:85105163425
VL - 12
IS - 1
M1 - 2496
ER -