奖励性记忆改善焦虑的细胞分子基础研究

Anxiety is a prevalent psychological disorder, and influences social activity in patient life. The side-effect of anxiolytic drugs makes psychological desensitization to be widely used. The desensitization therapy is more or less fulfilled through a process that positive memory reduces over-elevated attention and social phobia, such that we hypothesize a memory-mediated anxiety improvement. Our current study indicates that the rewarded working memory improves anxiety and upregulates synaptic plasticity. A key scientific issue is cellular and molecular mechanisms underlying memory-mediated anxiety improvement. Through combining our new animal models of associative learning with multiple disciplinary approaches, such as behavioral tasks, cell imaging, electrophysiology and molecular genetics, we aim to address the following questions, including how the different types of associative memory and their combinations are able to improve anxiety efficiently, how cerebral excitatory and inhibitory neurons coordinately fulfill memory formation and anxiety improvement, how circuitry connectomics among distinct cerebral areas undergoes plasticity for memory formation and anxiety improvement, and what are the molecular mechanisms for memory-mediated anxiety improvement in terms of cell-type specificity. Our studies will provide the experimental evidences for finding more efficient approaches of memory-mediated anxiety improvement as well as addressing their cellular and molecular mechanisms.

焦虑症是常见的精神疾病，严重影响患者的社会活动与生活。抗焦虑药物的副作用使得心理脱敏疗法得以重视，脱敏疗法在某种程度上是通过正性记忆缓解过度警觉。基于记忆改善焦虑之假说，我们的研究显示奖励性工作记忆能够改善焦虑状态和上调突触可塑性。拟解决的核心科学问题是正性记忆改善焦虑的细胞分子基础。结合我们新建的不同类型的联合式学习记忆的动物模型，以及行为分析、细胞成像、电生理和分子遗传等技术，该项目重点研究内容包括：1）不同类型联合式学习记忆及其组合改善焦虑的效率； 2）大脑兴奋和抑制性神经元如何协调储存信息和改善焦虑；3）联合式学习记忆改善焦虑的脑区间神经投射及其环路图谱；4）联合式学习记忆改善焦虑的细胞类型特异的分子机理。该研究将为建立有效地改善焦虑的学习记忆方法及其细胞分子原理提供实验基础。

“奖赏记忆改善焦虑的细胞分子基础研究(81471123)”项目的研究内容包括不同类型联合式学习记忆改善焦虑的效率；大脑兴奋和抑制性神经元如何协调储存信息和改善焦虑；联合式学习记忆改善焦虑的脑区间神经环路图谱；联合式学习记忆改善焦虑的细胞类型特异的分子机理。研究成果包括阐明了奖赏改善焦虑动物模型的蛋白激酶在突触可塑性中的作用；在新型联合学习动物模型阐明了联合记忆细胞工作原理；奖赏改善抑郁的基因表达谱和表观谱的动态变化。这些研究成果为阐明人类最基本和最重要的联合式学习模式以及多信息联合记忆的神经细胞环路基础提供理论模型和实验依据。研究成果发表在SCI收录的国际学术期刊Cerebral Cortex, Translational Psychiatry和 Frontiers in Cellular Neurosciences。