lncRNA13作为miR-876-5p的前体调节kcnn3基因表达参与病理性情感记忆形成的机制研究

毒品成瘾和创伤后应激障碍是目前严重的公共卫生和社会问题，二者共同的特征是在吸食毒品或遭遇灾难性事件后会产生强烈、持久的以奖赏或恐惧为特征的病理性情感记忆。目前，有关病理性情感记忆的神经生物学机制尚未完全明确。课题组前期研究发现伏隔核中lncRNA13可能作为miRNA的前体分子参与病理性情感记忆的形成过程，但其机制尚待继续阐明。本项目围绕奖赏性和恐惧性病理性情感记忆，在前期工作基础上，采用条件性位置偏爱模型、静脉自身给药模型、场景条件化恐惧模型和转录组学技术方法，首次探讨伏隔核lncRNA13-miR-876-5p-kcnn3 mRNA调控网络参与病理性情感记忆形成及突触可塑性改变过程的表观遗传调控机制。项目的开展可为毒品成瘾及创伤后应激障碍的诊断、鉴定和治疗提供新的分子标志物和干预靶点，丰富病理性情感记忆形成的表观遗传调控机制。

Drug addiction and post-traumatic stress disorder (PTSD) are serious public health and social problems, both of which are characterized by strong and persistent pathological emotional memory induced by drug use or catastrophic events. At present, the neurobiological mechanism of pathologic emotional memory is not completely clear. Our previous study found that lncRNA13, as a precursor molecule of miRNA, in the nucleus accumbens may be involved in the formation of pathological emotional memory, but its mechanism remains to be clarified. Based on previous works, this project will focus on reward and fear context conditioned emotional memory, and using the conditioned place preference, intravenous self-administration and the context conditioned fear model, as well as transcriptome technological methods to explore the epigenetic regulatory mechanism of lncRNA13-miR-876-5p-kcnn3 mRNA network in nucleus accumbens for pathological emotional memory formation and synaptic plasticity changes. The development of this project can provide new molecular markers and intervention targets for the diagnosis, identification and treatment of drug addiction and post-traumatic stress disorder, and can enrich the epigenetic regulatory mechanism for the formation of pathological emotional memory.