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光遗传学破坏睡眠连续性会损害记忆巩固。

Optogenetic disruption of sleep continuity impairs memory consolidation.

机构信息

Departments of Psychiatry and Behavioral Science and Biology, Stanford University, Stanford, CA 94305-5020, USA.

出版信息

Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13305-10. doi: 10.1073/pnas.1015633108. Epub 2011 Jul 25.

Abstract

Memory consolidation has been proposed as a function of sleep. However, sleep is a complex phenomenon characterized by several features including duration, intensity, and continuity. Sleep continuity is disrupted in different neurological and psychiatric conditions, many of which are accompanied by memory deficits. This finding has raised the question of whether the continuity of sleep is important for memory consolidation. However, current techniques used in sleep research cannot manipulate a single sleep feature while maintaining the others constant. Here, we introduce the use of optogenetics to investigate the role of sleep continuity in memory consolidation. We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity. Fragmenting sleep after the learning phase of the novel object recognition (NOR) task significantly decreased the performance of mice on the subsequent day, but memory was unaffected if the average duration of sleep episodes was maintained at 62-73% of normal. These findings demonstrate the use of optogenetic activation of arousal-related nuclei as a way to systematically manipulate a specific feature of sleep. We conclude that regardless of the total amount of sleep or sleep intensity, a minimal unit of uninterrupted sleep is crucial for memory consolidation.

摘要

记忆巩固被认为是睡眠的一项功能。然而,睡眠是一种复杂的现象,具有几个特征,包括持续时间、强度和连续性。睡眠连续性在不同的神经和精神疾病中受到破坏,其中许多疾病伴随着记忆缺陷。这一发现引发了一个问题,即睡眠的连续性是否对记忆巩固很重要。然而,目前用于睡眠研究的技术无法在保持其他特征不变的情况下,单独操纵睡眠的一个特征。在这里,我们介绍了使用光遗传学来研究睡眠连续性在记忆巩固中的作用。我们用光遗传学靶向下丘脑分泌素/食欲素神经元,这些神经元在觉醒过程中发挥关键作用。我们在行为小鼠中以不同的间隔用光遗传学激活这些神经元,能够在不影响其总时长或强度的情况下,使睡眠碎片化。在新物体识别(NOR)任务的学习阶段之后,将睡眠碎片化会显著降低小鼠在随后一天的表现,但如果将睡眠片段的平均持续时间维持在正常水平的 62-73%,则记忆不受影响。这些发现表明,使用光遗传学激活与觉醒相关的核团是一种系统地操纵睡眠特定特征的方法。我们得出结论,无论睡眠的总时长或强度如何,最小的不间断睡眠单元对于记忆巩固都是至关重要的。

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