Department of Anatomy, College of Preclinical Medicine, Dali University, Dali, China.
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
Exp Neurol. 2022 Dec;358:114224. doi: 10.1016/j.expneurol.2022.114224. Epub 2022 Sep 9.
Memory extinction and renewal are major factors that limits the efficacy of exposure therapy. The dorsal dentate gyrus (dDG) plays a crucial role in spatial memory, and epigenetic modifications in the dDG play an important role in fear memory renewal. However, whether dDG activity regulates fear memory extinction and renewal remains unclear. In this study, we showed that an extinction procedure that prevents fear memory renewal (extinction within the reconsolidation window) leads to increased c-fos expression in the dDG. Chemicogenetic activation of dDG excitatory neurons during extinction training elevated fear memory extinction and prevented renewal, whereas inhibition of dDG excitatory neurons inhibited fear memory extinction. We also demonstrated that inhibiting fear engram cells (neurons active during fear acquisition) during extinction training inhibits fear memory extinction. Therefore, dDG activity during fear extinction plays an important role in fear memory extinction and renewal.
记忆的消退和更新是限制暴露疗法疗效的主要因素。背齿状回（dDG）在空间记忆中起着关键作用，而 dDG 中的表观遗传修饰在恐惧记忆更新中起着重要作用。然而，dDG 活动是否调节恐惧记忆的消退和更新尚不清楚。在这项研究中，我们表明，一种阻止恐惧记忆更新的消退程序（在再巩固窗口内的消退）会导致 dDG 中的 c-fos 表达增加。在消退训练期间化学遗传学激活 dDG 兴奋性神经元会提高恐惧记忆的消退并阻止其更新，而抑制 dDG 兴奋性神经元会抑制恐惧记忆的消退。我们还证明，在消退训练期间抑制恐惧记忆形成细胞（在恐惧获得期间活跃的神经元）会抑制恐惧记忆的消退。因此，恐惧消退期间 dDG 的活动在恐惧记忆的消退和更新中起着重要作用。
