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成年海马神经发生缺失小鼠的非快速眼动睡眠破坏和与睡眠相关的空间记忆巩固。

Disruption of NREM sleep and sleep-related spatial memory consolidation in mice lacking adult hippocampal neurogenesis.

机构信息

Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72076, Tübingen, Germany.

Department of Psychiatry and Psychotherapy, University Hospital Tübingen, 72076, Tübingen, Germany.

出版信息

Sci Rep. 2020 Oct 5;10(1):16467. doi: 10.1038/s41598-020-72362-3.

Abstract

Cellular plasticity at the structural level and sleep at the behavioural level are both essential for memory formation. The link between the two is not well understood. A functional connection between adult neurogenesis and hippocampus-dependent memory consolidation during NREM sleep has been hypothesized but not experimentally shown. Here, we present evidence that during a three-day learning session in the Morris water maze task a genetic knockout model of adult neurogenesis (Cyclin D2) showed changes in sleep macro- and microstructure. Sleep EEG analyses revealed a lower total sleep time and NREM fraction in Cyclin D2 mice as well as an impairment of sleep specific neuronal oscillations that are associated with memory consolidation. Better performance in the memory task was associated with specific sleep parameters in wild-type, but not in Cyclin D2 mice. In wild-type animals the number of proliferating cells correlated with the amount of NREM sleep. The lack of adult neurogenesis led to changes in sleep architecture and oscillations that represent the dialog between hippocampus and neocortex during sleep. We suggest that adult neurogenesis-as a key event of hippocampal plasticity-might play an important role for sleep-dependent memory consolidation and modulates learning-induced changes of sleep macro- and microstructure.

摘要

细胞在结构水平上的可塑性和行为水平上的睡眠对记忆形成都是必不可少的。两者之间的联系尚未得到很好的理解。人们假设,在非快速眼动睡眠期间,成年神经发生和海马依赖性记忆巩固之间存在功能联系,但尚未通过实验证明。在这里,我们提供的证据表明,在 Morris 水迷宫任务的三天学习过程中,成年神经发生的基因敲除模型(Cyclin D2)显示出睡眠宏观和微观结构的变化。睡眠 EEG 分析显示,Cyclin D2 小鼠的总睡眠时间和 NREM 分数较低,与记忆巩固相关的特定睡眠神经元振荡受损。在野生型动物中,记忆任务的更好表现与特定的睡眠参数相关,但在 Cyclin D2 小鼠中则没有。在野生型动物中,增殖细胞的数量与 NREM 睡眠的量相关。缺乏成年神经发生导致睡眠结构和振荡发生变化,这些变化代表了海马体和新皮层在睡眠期间的对话。我们认为,成年神经发生作为海马体可塑性的关键事件,可能在睡眠依赖性记忆巩固中发挥重要作用,并调节学习引起的睡眠宏观和微观结构的变化。

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