NREM睡眠在联合型运动记忆巩固中的作用及其前额叶皮层重激活机制研究

Associative motor memory is one of advanced brain functions which are necessary for the survival human being in varying environment. It has been reported that the consolidation of associative motor memory is significantly impaired in the patients with prolonged wakefulness or abnormal mental state. However, the key mechanisms underlying these changes remain unclear. The medial prefrontal cortex.is an important brain area for the consolidation of associative motor memory, and persistent activity of pyramidal cells in this area is critically involved in the memory process. Based on our preliminary results that post-learning NREM sleep is specifically involved in motor memory consolidation, our present project aims to further investigate reactivation of persistent activity cells in the post-learning NREM sleep. Moreover, we will determine the contribution to reactivation of persistent activity cells to neural plasticity in the prefrontal cortex and the consolidation of associative motor memory. At last, we will explore whether impaired motor memory can be rescued by functional potentiation of the reactivation of persistent activity cells after the prolonged wakefulness. To this end, several techniques are utilized, including multiple units recording, optogenetics, patch clamp recording, and behavioral tests. The outcomes from this project will provide new insights into relieving the impaired associative motor memory induced by the prolonged wakefulness .

联合型运动记忆是人在不断变化的环境中生存所必需的脑高级功能。近期发现觉醒状态异常或精神疾病状态下，联合型运动记忆的巩固能力显著降低，但其中的关键机制仍不清楚。内侧前额叶皮层是联合型运动记忆巩固发生的关键脑区，该区锥体神经元的持续性放电是表征联合型运动记忆巩固的重要神经活动。本项目拟在前期发现“学习后NREM睡眠特异参与联合型运动记忆巩固”的基础上，以内侧前额叶皮层的持续性放电神经元为研究对象，采用在体多通道记录、光遗传学、膜片钳记录和整体行为学等技术，研究NREM睡眠期内侧前额叶皮层持续性放电神经元的重激活特征，明确重激活对持续性放电神经元活动可塑性和联合型运动记忆巩固的影响及神经环路机制，并初步探讨延长觉醒后联合型运动记忆巩固能力维持的调控方法，以期能够全面阐明联合型运动记忆巩固的生理学基础，最终为延长觉醒应激条件下该功能的适应性维持提供环路和细胞水平的新思路。

联合型运动记忆是人在不断变化的环境中生存所必需的脑高级功能。近期研究发现觉醒状态异常或精神疾病状态下，联合型运动记忆的巩固能力显著降低，但其中的关键机制仍不清楚。内侧前额叶皮层是联合型运动记忆巩固发生的关键脑区，该区锥体神经元的持续性放电是表征联合型运动记忆巩固的重要神经活动。本项目利用在体多通道记录、光遗传学和整体行为学等实验技术，研究了NREM睡眠期间前额叶皮层神经元重激活与海马尖波涟漪波振荡之间的耦合关系及其生理作用。所得研究结果初步明确了内侧前额叶皮层中不同类型的神经元在联合型运动记忆训练过程中的放电活动特征及作用，并评估了NREM睡眠期间内侧前额叶皮层神经元重激活与海马尖波涟漪波振荡之间的联合型运动记忆信息传递特征，揭示了联合型运动记忆巩固的神经网络活动基础。此外，还拓展性探究了海马中间神经元在联合型运动记忆过程中的活动特征及其作用、以及作为内侧前额叶皮层下游的小脑神经元在联合型运动记忆中的作用及其机制。所得结果为全面阐明NREM睡眠促进联合型记忆巩固的生理机制提供了重要新启示，也渴望为后期改善睡眠剥夺或延长觉醒所致的联合型运动记忆巩固损害症状提供新的理论依据。