Sex differences in fear memory consolidation via Tac2 signaling in mice

• Published in: Nature communications Vol. 12; no. 1; pp. 2496 - 19
• Main Authors: Florido, A., Velasco, E. R., Soto-Faguás, C. M., Gomez-Gomez, A., Perez-Caballero, L., Molina, P., Nadal, R., Pozo, O. J., Saura, C. A., Andero, R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-05-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 17β-Estradiol; 38/1; 42; 45; 45/77; 59; 631/378/1457/1284; 631/378/1595/1395; 631/378/1595/2636; 64/60; 692/308/2778; 82/51; 82/58; 82/80; 96; AKT protein; Amygdala; Animal behavior; Animal memory; Animals; Antipsychotic Agents - pharmacology; Central Amygdaloid Nucleus - physiology; Conditioning, Classical - physiology; Consolidation; Estradiol - metabolism; Estrus cycle; Fear; Fear & phobias; Fear - physiology; Female; Females; Gender aspects; Humanities and Social Sciences; Male; Males; Medical treatment; Memory Consolidation - physiology; Mental disorders; Mental health; Mice; Mice, Inbred C57BL; multidisciplinary; Phobias; Piperidines - pharmacology; Post traumatic stress disorder; Protein Precursors - antagonists & inhibitors; Protein Precursors - metabolism; Psychological stress; Science; Science (multidisciplinary); Sex; Sex differences; Sex Factors; Sex hormones; Signal Transduction; Signaling; Tachykinin; Tachykinin receptors; Tachykinins - antagonists & inhibitors; Tachykinins - metabolism; Testosterone; Testosterone - metabolism; β-Catenin
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22911-9

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/GSK3β/β-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.