心理应激是理想需求与实际满足存在巨大差异所致的机体心理和生理反应，可影响个体的情绪及认知功能。其所致认知功能损伤的分子生物学机制一直以来都是医学和神经科学领域研究的热门问题。Npas4 (Neuronal Per-Arnt-Sim domain protein 4) 是一个学习记忆形成的关键转录因子，且表达量易受应激行为影响，提示其可能在心理应激致认知功能障碍中发挥重要作用。本课题前期通过改良的旁观电击建立心理应激致认知功能障碍动物模型，发现模型小鼠海马区Npas4表达量显著降低。基于前期成果，本课题拟以Npas4基因着手，从动物、细胞和分子水平，利用基因工程技术、神经行为学、神经生物学、神经电生理、病毒学、细胞生物学和分子生物学的方法，阐明心理应激调控Npas4表达的分子机制，探讨Npas4基因在心理应激致认知功能障碍中的作用和机理，为防治心理应激致认知功能障碍提供理论依据和药物靶点。

Psychological stress is the mental and physiological response caused by the huge difference between ideal demand and actual situation, which could affect the individual's emotions and cognitive functions. The molecular biological mechanism of cognitive dysfunction caused by psychological stress has always been a popular topic in the fields of medicine and neuroscience. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a key transcription factor for learning and memory formation, and its expression is susceptible to stress, suggesting that it may play an important role in psychological stress induced cognitive dysfunction. Previously, a cognitive dysfunction animal model was established by psychological stress caused by a communication box. The expression of Npas4 in the hippocampus of the model mice was significantly reduced. Based on the results of previous research, this study aims to elucidate the molecular mechanism of Npas4 expression regulated by psychological stress and to investigate the role of Npas4 gene in cognitive dysfunction caused by psychological stress at the animal, cellular and molecular levels, using the following methods including genetic engineering techniques, neurobehavioral, neurobiology, neuroelectrophysiology, virology, cell biology and molecular biology. And finally, the theoretical basis and drug target for the prevention and treatment of psychological stress induced cognitive impairment can be provided.