0073 Investigating the epigenetic mechanisms underlying memory consolidation during sleep

Abstract

Abstract Introduction It has been established that sleep after learning something (“post-learning sleep”) actively consolidates what was learned. Yet, the underlying cellular and molecular mechanisms are undergoing active investigation. The fear conditioning (FC) memory paradigm, in which an animal learns to associate an environmental cue to an aversive foot shock, has been widely used for memory investigation. While amygdala and hippocampus are two critical sites for processing and storing the FC memory, how the amygdala consolidate this memory during sleep, from both cellular and molecular perspectives, has been little understood, compared to the hippocampus. Moreover, one potential molecular substrate of memory, DNA methylation, has been studied in the hippocampus for its role in learning and memory. Yet it is little known for its memory role in the BLA. Methods Here, we used fiber photometry, miniscope calcium imaging, EEG recording, optogenetic manipulation, and whole genome bisulfite sequencing to study the neural mechanisms underlying memory consolidation in the basolateral amygdala (BLA) during sleep. Results (1) We found that the BLA neurons display increased activity during REM sleep, compared to that in non-REM (NREM) sleep. (2) Using closed-loop optogenetic strategy, our preliminary results showed that silencing BLA activity during REM sleep leads to memory impairment in contextual fear conditioning task. (3) We compared DNA methylation of BLA neurons at a whole genome level between mice with and without sleep after FC learning and identified differentially methylated regions between them. Conclusion Together, our data suggests that the BLA activity during REM sleep is required for consolidation of fear memory, and DNA methylation might mediate this process. Support (if any)