表观遗传学机制是神经科学领域近年来研究的一个热点，尤其是学习记忆的表观遗传学对认知功能影响的机制越来越激发起人们的兴趣。组蛋白翻译后修饰（乙酰化、甲基化、磷酸化等）的表观遗传调控成为认知记忆过程的重要调节方式，而组蛋白乙酰化和促进记忆形成的关系最为密切。ERK1/2 MAPKs在调控学习记忆的表观遗传学改变中发挥重要作用，是突触可塑性和经历所致行为改变调控组蛋白翻译后修饰的中心环节。IQGAP1是MAPKs的脚手架蛋白，在ERK1/2的激活中发挥重要作用。我们先前的研究表明IQGAP1在海马依赖的学习记忆中发挥重要作用，但是否通过组蛋白翻译后修饰影响记忆的形成还不得而知。本课题将在分子、细胞和整体水平，研究IQGAP1/ERK信号通路对海马依赖的学习记忆认知功能的表观遗传学的影响及机制，将有助于了解诸如阿尔茨海默病（AD）、术后认知功能障碍（POCD）等认知功能障碍的机制并探索新的治疗途径。

Epigenetic mechanisms in learning and memory are in particularly interesting in neuroscience recently. Of the several types of epigenetic modifications that have been associated with cognitive functions - including posttranslational modification of histone proteins by acetylation, methylation and phosphorylation - histone acetylation is most robustly associated with promoting memory formation. ERK1/2 MAPKs are central to controlling histone posttranslational modifictions in synaptic plasticity and experience-driven behavioral changes. IQGAP1, a scaffold protein of MAPKs, is involved in activation of ERK1/2. Our previous studies have demonstrated that IQGAP1 is critical for hippocampus-dependent learning and memory. But it's not known whether histone posttranslational modifications is regulated by IQGAP1/ERK signal pathway. In this study we will clarify the epigenetic mechanisms in cognition for IQGAP1/ERK signal pathway on hippcampus-dependent learning and memory with molecular, cellular and behavioral methods. This will help us to understand the mechanisms of cognitive deficits such as Alzheimer's Disease(AD), Postoperative Cognitive Dysfuction(POCD) and find new therapeutic strategy.