髓鞘形成在睡眠促进空间记忆巩固中的作用及机制研究

睡眠减少导致空间记忆损害。神经元重激活被认为是睡眠促进空间记忆巩固的关键机制。目前认为，尖波涟漪波(SWR)是海马神经元重激活的重要载体，它依赖于海马锥体细胞与中间神经元的高时间精度相互作用，但该作用的保障机制不清楚。结合文献和项目组前期发现，中枢神经系统髓鞘形成是记忆巩固所必需。鉴于已知髓鞘具有保障轴突动作电位精确传导的功能，我们提出假说：睡眠期海马锥体细胞重激活促进髓鞘形成，而新的髓鞘形成又保障海马锥体细胞与中间神经元的高时间精度相互作用，使SWR正常发生并促进空间记忆巩固。本项目拟结合多通道记录、光遗传学、环路示踪、形态学和行为学技术，证明睡眠期海马锥体细胞重激活与髓鞘形成之间的因果关系，揭示髓鞘形成在海马SWR发生和空间记忆巩固中的作用，探讨调控髓鞘形成改善睡眠剥夺后空间记忆巩固的效果。这有助于完整揭示睡眠促进空间记忆巩固的机制，更可为缓解睡眠剥夺应激条件下空间记忆损害提供新思路。

Reduced sleep results in the impairment of spatial memory. It has been suggested that neuronal reactivation in the hippocampus is one of the critical mechanism underlying sleep-promoting spatial memory consolidation. It is generally accepted that sharp wave ripple (SWR) is the carrier of neuronal reactivation, which relies highly on the high precision interaction between the pyramidal cells and interneurons in the hippocampus. Nevertheless, how the high precision interaction is ensured remains unclear. Based on recent studies performed by others and us, it has been demonstrated that myelination in central nervous system is necessary for the consolidation of memory consolidation. In addition, it has been shown that myelin sheath has the ability to ensure the fast propagation of axonal action potential with high temporal precision. Therefore, we hypothesize that hippocampal neuronal reactivation enhances myelination during sleep. Afterwards, the enhanced myelination ensures high temporal precision interaction between the pyramidal cells and interneurons, so as to maintain the production of hippocampal SWR and enhance spatial memory consolidation. To this end, we combine several techniques, including multiple units recording, optogenetics, immunofluorescence staining, neuronal circuit tracing and behavioral tests, to demonstrate the causal relationship between hippocampal neuronal reactivation and myelination. We also aim to investigate the role of myelination in the production of SWR and spatial memory consolidation. Moreover, we will test whether enhancement of the myelination can rescue the impaired spatial memory after sleep deprivation. The outcomes from this project will shed new insights into the neural mechanism underlying the consolidation of spatial memory during sleep. More importantly, it may provide new hints on how to relieve the impaired memory consolidation induced by sleep deprivation.