DYRK1A modulates fear memory formation via epigenetic modification

초록

Fear memory formation is crucial for survival, with the hippocampus playing a central role. This study examines behavioral and molecular aspects of fear memory formation, focusing on Dual-specificity tyrosine regulated kinase 1A (DYRK1A). We found that DYRK1A expression in hippocampal CA1 pyramidal neurons is downregulated after contextual fear conditioning (CFC). To investigate the functional implications of this change, we found decreased DYRK1A binding to the MAO-A promoter following CFC, suggesting a role for DYRK1A in transcriptional regulation during fear memory formation. DYRK1A overexpression reduced freezing behavior, while knockdown enhanced it. At the molecular level, DYRK1A overexpression increased trimethylated histone 3 Lys 4 (H3K4me3) levels, an active promoter marker, while knockdown decreased H3K4me3. These findings suggest that DYRK1A modulates fear memory formation through epigenetic regulation, likely altering gene expression via histone modifications. This research highlights DYRK1A's nuclear roles and its potential as a target for neuropsychiatric disorders related to fear and memory.