Identification of flap structure specific endonuclease 1 as a factor involved in LTM formation of aversive learning

We proposed that DNA recombination/repair processes play a role in memory formation. Here, we used microarray analysis of rat amygdala genes to identify possible DNA recombination/repair factors involved in memory consolidation of conditioned taste aversion (CTA). Among the genes that showed statistically significant differential expression, we identified fen-1, encoding a flap-structure specific DNA endonuclease. Amygdalar fen-1 mRNA induction was associated to the illness component of CTA, since it could be observed by the pairing of a flavor and gastrointestinal illness, by the illness itself, but not by the presentation of the flavor alone. No CTA related induction of fen-1 expression was observed in the insular cortex. Importantly, functional validation studies demonstrated that amygdalar suppression of fen-1 expression impaired memory consolidation of CTA. Overall, our studies helped identify a new DNA recombination/repair candidate factor involved in memory formation of aversive experiences.本研究提出，DNA重组/修复（DNA recombination/repair）过程在记忆形成中发挥作用。本研究通过对大鼠杏仁核基因开展微阵列（microarray）分析，旨在筛选参与条件性味觉厌恶（conditioned taste aversion, CTA）记忆巩固过程的潜在DNA重组/修复相关因子。在呈现统计学显著性差异表达的基因中，我们鉴定出fen-1，其编码一种flap结构特异性DNA核酸内切酶（flap-structure specific DNA endonuclease）。杏仁核中fen-1的mRNA诱导表达与条件性味觉厌恶的疾病相关组分密切相关：该诱导可通过味觉刺激与胃肠道疾病的配对刺激、以及单独的疾病刺激触发，但仅单独呈现味觉刺激则无法诱导该表达。在岛叶皮层（insular cortex）中，未观察到与条件性味觉厌恶相关的fen-1表达诱导现象。尤为重要的是，功能验证实验证实，抑制杏仁核中fen-1的表达会损害条件性味觉厌恶的记忆巩固过程。综上，本研究成功鉴定出一种参与厌恶性经历记忆形成的新型DNA重组/修复候选因子。