The role of BAF53b in fear memory persistence

Abstract

Much has been known about molecules and mechanisms involved in memory consolidation. However, relatively less is known about what supports the persistence of once consolidated 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 tested 24 hours post-learning. In this study, we report a delayed induction of BAF53b in the LA at 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.