Endurance represents a highly adaptive function of fear memory and a major cause of maladaptive fear- and anxiety-related mental disorders. However, less is known about the mechanisms underlying the persistence of fear memory. The epigenetic gene regulation recently emerged as an important mechanism for memory persistence. In the previous study, we found that BAF53b, a neuron-specific subunit of BAF chromatin remodeling complex, is induced after auditory cued fear conditioning in the lateral amygdala (LA) and is crucial for recent fear memory formation. In this study using mice of both sexes, we report a delayed induction of BAF53b in the LA 48 h after auditory fear conditioning and its critical role for the persistence of established fear memory. To specifically block the delayed but not the early induced BAF53b function, we used a postlearning knock-down method based on RNAi. The transient knockdown of Baf53b using siRNA in the lateral amygdala 24 h after cued fear conditioning led to specific impairment of remote but not recent memory retrieval. RNA-sequencing analyses identified fibroblast growth factor 1 (FGF1) as a candidate downstream effector. Consistently, postlearning administration of FGF1 peptide rescued memory persistence in Baf53b knock-down mice. These results demonstrate the crucial role of BAF53b and FGF1 in persistent retention of fear memory, giving insights into how fear memory persistently stored through consolidation processes and suggest candidate target for treating mental disorders related to traumatic memory.

SIGNIFICANCE STATEMENT It is still unclear how once consolidated memory persists over time. In this study, we report the delayed induction of nucleosome remodeling factor BAF53b in the lateral nucleus of amygdala after fear learning and its crucial role for persistence of established memory beyond 24 h after learning. Our data link the regulation of BAF53b and fibroblast growth factor 1 expression in the amygdala to fear memory persistence. Results from this study open a new direction to understand the time-dependent continuous consolidation processes potentially by a nucleosome-remodeling mechanism enabling long-lasting memory formation and give insights into how to treat mental disorders caused by enduring traumatic memory.

耐力代表恐惧记忆的高度适应性功能，是与适应不良的恐惧和焦虑相关的精神障碍的主要原因。然而，关于恐惧记忆持久性的潜在机制知之甚少。表观遗传基因调节最近已成为记忆持久性的重要机制。在先前的研究中，我们发现BAF53b是BAF染色质重塑复合体的神经元特异性亚基，是在听觉提示的外侧杏仁核（LA）的恐惧条件调节后诱导的，对最近的恐惧记忆形成至关重要。在这项使用雌雄同体小鼠的研究中，我们报道了在听觉恐惧条件调节后48小时内LAF53b的诱导延迟及其对持续建立恐惧记忆的关键作用。为了特异性阻断延迟但非早期诱导的BAF53b功能，我们使用了基于RNAi的学习后剔除方法。的瞬时击倒Baf53b在提示恐惧条件后24小时在外侧杏仁核中使用siRNA导致远端但近期记忆恢复没有特异性损伤。RNA测序分析确定成纤维细胞生长因子1（FGF1）为候选下游效应物。一致地，学习后施用FGF1肽可以挽救Baf53b敲除小鼠的记忆力。这些结果证明了BAF53b和FGF1在恐惧记忆的持久保留中起着至关重要的作用，从而洞悉了恐惧记忆如何通过巩固过程持久地存储，并为治疗与创伤记忆有关的精神障碍提供了候选靶点。

意义声明尚不清楚统一存储器如何随着时间持续存在。在这项研究中，我们报告了恐惧学习后杏仁核外侧核中核小体重构因子BAF53b的诱导延迟及其在学习后24 h内持久建立记忆的关键作用。我们的数据将杏仁核中BAF53b和成纤维细胞生长因子1表达的调节联系起来，以担心记忆持久性。这项研究的结果为理解可能依赖时间的连续巩固过程提供了新的方向，该过程可能通过核小体重塑机制实现持久的记忆形成，并为如何治疗由持久性创伤记忆引起的精神障碍提供了见识。