Insights into paradoxical (REM) sleep homeostatic regulation in mice using an innovative automated sleep deprivation method
Insights into paradoxical (REM) sleep homeostatic regulation in mice using an innovative automated sleep deprivation method
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DOI：
10.1093/sleep/zsaa003
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发表时间：
2020-07-01
期刊：
影响因子：
5.6
通讯作者：
Peyron, Christelle
中科院分区：
文献类型：
--
作者：
Arthaud, Sebastien;Libourel, Paul-Antoine;Peyron, Christelle
自发现矛盾睡眠（也称为快速眼动睡眠）以来，确定其激活的精确神经网络一直是一个挑战。同样，我们对调节PS的内稳态机制的理解仍然有限，无论是通过昼夜节律和超昼夜驱动的外部调制还是通过内在的内稳态调节，主要是由于干扰因素使研究变得困难。事实上，迄今为止发表的所有研究都无法在不显著改变慢波睡眠和/或压力水平的情况下操纵PS，因此在分析中引入了潜在的偏差。为了更好地理解PS稳态，我们开发了一种基于自动警觉状态评分的新方法——使用脑电图和肌电图特征——当检测到PS时，通过诱导笼底运动来闭环剥夺PS。在PS剥夺的6和48 h以及随后的恢复期，分析警惕性状态。使用这种新的自动化方法，我们能够在短时间或长时间内高效和特异性地剥夺小鼠的PS，观察不到应激迹象（通过血浆皮质酮水平和睡眠潜伏期评估），不需要人为干预或环境改变。我们在这里表明，PS可以自我调节和调节，而在慢波睡眠和清醒状态下没有引起显著的变化，PS反弹的持续时间取决于先前PS缺陷的数量。我们还发现，在剥夺PS的情况下，间歇持续时间与先前的PS发作持续时间无关。大量有争议的文献已经产生，试图揭示矛盾睡眠（REM睡眠）稳态调节的本质。在这些研究中，矛盾睡眠通过不同的方式受到挑战，使用完全睡眠剥夺，或多或少特定的PS剥夺，并且大多数时候会引起相当大的压力。在这里，我们报告使用一种创新的方法，允许高度特异性地剥夺小鼠的矛盾睡眠，而不显着改变其他警觉性状态，矛盾睡眠稳态调节仅取决于先前的矛盾睡眠不足量。更好地理解矛盾睡眠是如何被调节的，对于帮助治疗焦虑障碍等疾病的共病失调至关重要。
Identifying the precise neuronal networks activated during paradoxical sleep (PS, also called REM sleep) has been a challenge since its discovery. Similarly, our understanding of the homeostatic mechanisms regulating PS, whether through external modulation by circadian and ultradian drives or via intrinsic homeostatic regulation, is still limited, largely due to interfering factors rendering the investigation difficult. Indeed, none of the studies published so far were able to manipulate PS without significantly altering slowwave sleep and/or stress level, thus introducing a potential bias in the analyses. With the aim of achieving a better understanding of PS homeostasis, we developed a new method based on automated scoring of vigilance states-using electroencephalogram and electromyogram features-and which involves closed-loop PS deprivation through the induction of cage floor movements when PS is detected. Vigilance states were analyzed during 6 and 48 h of PS deprivation as well as their following recovery periods. Using this new automated methodology, we were able to deprive mice of PS with high efficiency and specificity, for short or longer periods of time, observing no sign of stress (as evaluated by plasma corticosterone level and sleep latency) and requiring no human intervention or environmental changes. We show here that PS can be homeostatically modulated and regulated while no significant changes are induced on slow-wave sleep and wakefulness, with a PS rebound duration depending on the amount of prior PS deficit. We also show that PS interval duration is not correlated with prior PS episode duration in the context of recovery from PS deprivation.Statement of SignificanceA large body of controversial literature has been produced trying to reveal the nature of paradoxical sleep (REM sleep) homeostatic regulation. In these studies, paradoxical sleep was challenged by different means, using total sleep deprivation, more or less specific PS deprivation, and most of the time inducing a fair amount of stress. Here we report using an innovative method allowing to highly specifically deprive mice of paradoxical sleep without significantly modifying other vigilance states, that paradoxical sleep homeostatic regulation depends only on the prior amount of paradoxical sleep deficit. Gaining a better understating on how paradoxical sleep is regulated is crucial in helping to treat its comorbid dysregulation in diseases such as anxiety disorders.