触觉丰富改善应激所致认知与焦虑障碍的环路机制

应激是多种精神疾病的重要风险因素，可损害认知功能并诱发焦虑障碍。然而，应激所致认知和焦虑障碍的机制有待明确。既往研究和本课题组前期工作表明，慢性应激可引起小鼠初级躯体感觉皮层及海马神经元激活异常。反之，触觉经历丰富可调节相关脑区活动并改善记忆、缓解焦虑。这提示应激和触觉丰富通过改变触觉信息加工相关环路的可塑性与功能调节认知和焦虑水平。本项目拟采用慢性应激和触觉丰富小鼠模型，结合活动依赖性神经元标记、跨突触神经环路示踪、化学遗传学和行为学等手段，解析以海马为重要节点的触觉整合环路，明确海马等脑区内触觉响应性神经元在学习、记忆和焦虑样行为中的作用，进而揭示触觉丰富改善认知与情绪并缓解慢性应激（尤其是早年应激）不良效应的环路和分子基础。本项目有望发现应激扰乱触觉信息整合进而损害记忆、诱发焦虑的神经生物学机制，明确触觉丰富缓解应激不良效应的效果，为应激相关精神疾病的发病机制和干预研究提供崭新思路。

Stress is a major risk factor for psychiatric disorders and can impair cognitive function and induce anxiety disorders. However, mechanisms of stress-induced cognitive deficits and anxiety disorders remain to be investigated. Previous studies and our preliminary work show that chronic stress abnormally activates neurons in the mouse primary somatosensory cortex and the hippocampus. Conversely, tactile experience enrichment modulates the activity of related brain regions, improves cognition and alleviates anxiety. These findings suggest that both stress and tactile enrichment can regulate cognition and anxiety by altering the plasticity and function of tactile information processing-related neural circuits. In the current project, we will use mouse models of chronic stress and tactile enrichment, and combine multiple approaches including functional labeling of activated neurons, trans-synaptic tracing of neural circuits, chemogenetics, and behavioral analyses. We aim to understand tactile integration-related circuit(s) with the hippocampus as a key component, identify the roles of touch-responsive neurons in the hippocampus and related brain regions in learning, memory and anxiety-related behavior, and further reveal the circuit and molecular basis of the impact of tactile enrichment on cognition, emotion and chronic stress (especially early-life stress)-induced adverse effects. This project will unravel the neurobiological underpinnings on how stress impairs memory and induces anxiety by disrupting tactile integration, evaluate the effectiveness of tactile enrichment to ameliorate stress-induced detrimental consequences, and provide novel insight into the pathogenesis and intervention of stress-related psychiatric disorders.