Persistence of Fear Memory Depends on a Delayed Elevation of BAF53b and FGF1 Expression in the Lateral Amygdala

Abstract

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 post-learning 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.