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Updated: Aug 27, 2025
Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice
Published on: March 1, 2014
Genes and pathways associated with fear discrimination identified by genome-wide DNA methylation and RNA-seq analyses
Bo Hao1, Bu-Fang Fan2, Can-Can Cao2
1Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-sen University, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, China.
Abstract:
Fear memory is critical for individual survival. However, the maladaptive fear response is one of the hallmarks of fear-related disorders, which is characterized by the failure to discriminate threatening signals from neutral or safe cues. The biological mechanisms of fear discrimination remain to be clarified. In this study, we found that the nucleus accumbens (NAc) was indispensable for the formation of cued fear memory in mice, during which the expression of DNA methyltransferase 3a gene (DNMT3a) increased. Injection of Zebularine, a nonspecific DNMT inhibitor, into NAc immediately after conditioning induced a maladaptive fear response to neutral cue (CS-). Using whole-genome bisulfite sequencing (WGBS), differentially methylated sites and methylated regions (DMRs) were investigated. 16,226 DMRs in the genenome were identified, in which, 214 genes with significant differences in their methylation levels and mRNA expression profiles were identified through correlation analysis. Notably, 15 genes were synaptic function-related and 8 genes were enriched in the cGMP-PKG signaling pathway. Moreover, inhibition of PKG impaired fear discrimination. Together, our results revealed the profile and role of genome-wide DNA methylation in NAc in the regulation of fear discrimination.
