Sex differences in fear memory consolidation via Tac2 signaling in mice.

Sex differences in fear memory consolidation via Tac2 signaling in mice.
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DOI:
10.1038/s41467-021-22911-9
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发表时间:
2021-05-03
影响因子:
16.6
通讯作者:
Andero R
Andero R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Florido A;Velasco ER;Soto-Faguás CM;Gomez-Gomez A;Perez-Caballero L;Molina P;Nadal R;Pozo OJ;Saura CA;Andero R

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记忆的形成是大脑运作的关键。揭示记忆机制有助于我们更好地了解健康和疾病中的神经过程。此外,对创伤后应激障碍和恐惧症等与恐惧相关的疾病进行更具体的治疗,可能有助于减少它们对心理健康的负面影响。在这方面,中央杏仁核(CEA)中的速激肽2(Tac2)通路已被证明是调节恐惧记忆巩固的充分和必要的途径。CEA-TAC2拮抗作用及其药物遗传时间抑制作用削弱雄性小鼠的恐惧记忆。令人惊讶的是,我们在这里展示了Tac2阻滞剂在增强女性恐惧记忆巩固方面的相反效果。此外,我们还发现,男性的CEA-睾丸酮、女性的CEA-雌二醇以及Akt/GSK3Tac2-连环蛋白信号都介导了恐惧记忆的异性差异β/β通路的调节。中央杏仁核中的速激肽2(Tac2)通路对于调节恐惧记忆的巩固是充分和必要的。作者发现,抑制雄性小鼠杏仁核中的Tac2神经元可以减少恐惧的表达,而雌性小鼠在发情前期进行操作时,恐惧的表达会增加。
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.
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