DNA BASE MODIFICATIONS IN NEURAL PLASTICITY AND NEUROPSYCHIATRIC DISORDERS

描述（由申请人提供）：尽管基因表达的表观遗传调控已被证明与经验依赖的神经可塑性和记忆形成有关，但由于技术和概念的限制，DNA碱基修饰的全部功能及其在神经精神疾病中的作用仍然不明确。在本项目中，将开发新技术，以更精确地识别通过学习选择性激活的神经元群体中活性依赖的表观遗传机制，并挑战当前有关DNA碱基修饰的完整库及其在调节基因表达中的作用的概念。具体而言，我们将确定各种DNA碱基修饰与快速行为适应之间是否存在因果关系，并将在恐惧相关焦虑障碍的临床前模型中推进关于记忆的分子机制的知识状态。

DESCRIPTION (provided by applicant): Although epigenetic regulation of gene expression has been shown to be associated with experience- dependent neural plasticity and memory formation, due to technical and conceptual limitations, the full repertoire of DNA base modifications and their role in neuropsychiatric disease remains equivocal. In this project, new technology will be developed to more precisely identify activity-dependent epigenetic mechanisms in neuronal populations selectively activated by learning and challenge current concepts related to the full repertoire of DNA base modifications and their role in regulating gene expression. Specifically, we will determine whether there is a causal relationship between various DNA base modifications and rapid behavioral adaptation, and we will advance the state of knowledge regarding the molecular mechanisms underlying the memory in a preclinical model of fear-related anxiety disorder.