Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams

29/10/2026

AI Summary

Fear learning induces coordinated CpG and CpH DNA methylation remodelling specifically in basolateral amygdala engram neurons.
Post-learning sleep deprivation partially reverses engram methylation changes and impairs contextual fear memory recall.
Multi-omic atlas identifies Mid1 as a learning and sleep-regulated methylation target; Mid1 knockdown impairs fear memory consolidation.

TL;DR (AI Generated)

Using activity-dependent tagging and sequencing, we profiled the DNA methylome and transcriptome of engram and non-engram nuclei from the basolateral amygdala (BLA) after contextual fear conditioning with and without post-learning sleep deprivation.

Fear learning induces coordinated CpG and CpH DNA methylation remodeling specifically in engram neurons, with each showing unique temporal dynamics, revealing CpH methylation as a separate component of the engram's epigenetic signature.

Integrating the engram methylome with single-cell transcriptome profiling, we construct a multi-omic molecular atlas of the BLA fear engram and identify Mid1 as a learning- and sleep-regulated methylation target.

Basic summary

Cell Rep. 2026 Oct 28;45(11):118190. doi: 10.1016/j.celrep.2026.118190. Online ahead of print.

ABSTRACT

How sleep consolidates fear memories at the molecular level within individual engram neurons is unknown. Using activity-dependent tagging and sequencing, we profiled the DNA methylome and transcriptome of engram and non-engram nuclei from the basolateral amygdala (BLA) after contextual fear conditioning with and without post-learning sleep deprivation. Fear learning induces coordinated CpG and CpH DNA methylation remodeling specifically in engram neurons, with each showing unique temporal dynamics, revealing CpH methylation as a separate component of the engram’s epigenetic signature. Interestingly, sleep deprivation partially reverses learning-induced methylation changes and impairs memory recall, indicating that sleep supports engram-specific epigenetic consolidation. Integrating the engram methylome with single-cell transcriptome profiling, we construct a multi-omic molecular atlas of the BLA fear engram and identify Mid1 as a learning- and sleep-regulated methylation target. BLA-wide and engram-specific Mid1 knockdown establishes its functional requirement for fear memory consolidation, providing an approach to identify behaviorally relevant epigenetic targets.

PMID:42949914 | DOI:10.1016/j.celrep.2026.118190

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