Persistence of fear memory depends on a delayed elevation of BAF53b and FGF1 expression in the lateral amygdala.

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 mechanism of gene expression 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 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 hours after auditory fear conditioning and its critical role for the persistence of established fear memory. In order to specifically block the delayed but not early induced BAF53b function, we employed a post-learning knockdown method based on RNAi. The transient knockdown of BAF53b using siRNA in the lateral amygdala 24 hours after cued fear conditioning led to specific impairment of remote but not recent memory retrieval. RNA-seq analyses identified fibroblast growth factor 1 (FGF1) as a candidate downstream effector. Consistently, post-learning administration of FGF1 peptide rescued memory persistence in Baf53b knockdown 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 suggests candidate target for treating mental disorders related to traumatic memory. Significant 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 hours after learning. Our data link the regulation of BAF53b and fibroblast growth factor1 (FGF1) 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 nucleosome-remodeling mechanism enabling long-lasting memory formation and give insights into how to treat mental disorders caused by enduring traumatic memory.