Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams.

Contextual fear conditioning induces coordinated CpG and CpH DNA methylation remodeling specifically in basolateral amygdala (BLA) engram neurons, with CpH methylation forming a distinct epigenetic component.

• Why it matters: Sleep’s molecular role in consolidating fear memories within individual engram neurons is unclear, limiting understanding of how epigenetic states stabilize recall.
• What they did: Using activity-dependent tagging and sequencing, the study profiled DNA methylome and transcriptome of engram versus non-engram nuclei in BLA after fear conditioning with or without post-learning sleep deprivation.
• The result: Sleep deprivation partially reverses learning-induced methylation changes and impairs memory recall, and Mid1 knockdown in BLA-wide and engram-specific contexts is required for fear memory consolidation.