应激下情绪与记忆的认知神经机制

The adverse effects of stress on the brain and cognition have been recognized as one of the major risk factors of human health and disease. Understanding the neurocircuitry and its plastisticity of these effects has taken a great significance on the promotion of mental health. The overall goal of our proposed project is to identify core brain circuits, systems, and networks underlying adverse effects of stress on emotion and memory, as well as neurogenetics of individual differences in these effects and their plasticity. That is, to reveal the neural plasticity of the two key circuits: the" amygdala-ventromedial prefrontal (vmPFC) "circuit and the" hippocampus - vmPFC " circuit in anxiety and memory impairments under stress, and to establish the characteristic changes of the whole brain atlas in the emotional and memory brain network under stress. Outcomes of the proposed projects will provide crucial scientific basis to enhance individual's ability to deal with stress, intervention and treatment of stress-related mental disorders and health. The proposed research is expected to achieve at least 2 landmark achievements with international visibility, and publish more than 20 high-level papers in high-profile journals. The research team.consists of by six outstanding young researchers. The principal investigator (PI) has been awarded the "Outstanding Youth" project and the National key project of the NSFC. The team members has published over one hundred journal articles (SCI) in recent 5 years, including high-profile journals like Science, Nature Neuroscience, PNAS, Biological Psychiatry and The Journal of Neuroscience. The collaboration platform equipped with large-scale neuroscienctific equipment will also provide a strong guarantee in terms of academic, team, technology and.research platform.

应激对人类的生理功能、心理与行为活动有极大调节作用，是当前多学科交叉的重大前沿科学问题，与促进国民的心理健康水平密切相关。本项目将通过整合最新脑功能成像、基因和认知实验技术，在神经回路、系统、全脑、直至行为等多个层面上，揭示人类情绪与记忆的个体易感性特征及其基因基础，进而检验在“杏仁核—腹内侧前额叶”与“海马—腹内侧前额叶”等关键神经环路上的可塑性，建立应激条件下情绪与记忆网络特征变化的全脑图谱，从而为提高个体应激应对能力、干预和治疗应激相关精神障碍和身心疾病提供重要的科学依据。本项目拟完成2项有国际显示度的标志性成果，发表20篇以上有国际影响力的高水平论文。项目申请人先后负责基金委“杰青”和重点项目，项目组成员在近5年发表SCI论文上百篇，其中包括若干篇顶尖学术期刊论文。项目依托单位与合作单位已装备必要的认知神经科学设备，将在学术、队伍和技术等方面提供有力保证。

围绕“应激下情绪与记忆的认知神经机制”这一核心科学问题，项目组通过采用实验室诱发、重点人群采样、生理生化检测、遗传基因分型、多模态脑功能成像等技术，结合认知实验和计算模型，在基因-生理-神经环路-脑区活动-全脑网络-认知与心理行为等层面开展了一系列系统研究，阐明了急性应激、慢性应激等对情绪加工和记忆过程以及相关社会认知与情绪变化的关键作用机制与神经基础，揭示了杏仁核-前额叶、海马-前额叶以及皮层网络等多条关键神经通路在急性与慢性应激相关作用下的改变机制及其可塑性，利用双生子设计解析了核心通路受遗传与环境因素影响的发生发展与交互作用机制，刻画了应激相关情绪与情绪障碍的全脑功能网络连接模式与特征，建立了慢性应激与特质焦虑、急性应激相关状态焦虑的个体化预测模型，取得了一系列重要成果，为提高个体应激应对能力、干预和治疗应激相关精神障碍和身心疾病提供了重要的科学依据和实验基础。累计在Nature Communications, Biological Psychiatry, Neuroscience and Biobehavioral Reviews, Cerebral Cortex, Neuroimage, Brain Behavior and Immunity, Psychoneuroendocrinology, Translational Psychiatry, Human Brain Mapping等SCI/SSCI及中文核心期刊发表学术论文84篇；获教育部技术发明奖一等奖、广东省自然科学二等奖等科技奖励；申请专利10项。依托本项目，研究团队先后获批社科重大项目、国自然国际合作重点项目、优秀青年项目等国家、省市级项目31项，团队成员入选万人计划领军人才、基金委优秀青年基金、中国科协青年托举人才、博士后创新人才项目等；培养博士研究生20人、硕士研究生40人。开展了一系列卓有成效的国内外学术合作交流，包括举办了应激、情绪记忆、脑电与脑成像等国内外研讨会、特邀和专题报告20多场，引起了国内外专家同行的高度关注，受到了国内外媒体的广泛报道。项目组目前已与国内多家医院展开应用研究，实现焦虑障碍、抑郁症、精神分裂症等临床应用病例300余例，为应激相关障碍与疾病的临床诊断和治疗提供了直接指导和服务。本项目的系列研究成果将继续在临床障碍、特殊人群、国防军工等方面产生重要且广泛的影响。