Freitag Nicole, El-Tawil Kareem, Crane Aaron, Hilo Vanessa, Saad George, Eban-Rothschild Ada
Department of Psychology, University of Michigan, Ann Arbor, MI 48109, USA.
bioRxiv. 2025 Jun 3:2025.06.02.657276. doi: 10.1101/2025.06.02.657276.
In the period preceding sleep, humans and other animals display a stereotyped repertoire of behaviors-including hygiene-related activities and preparing a place to sleep. Evidence suggests that this pre-sleep phase actively contributes to sleep initiation and quality. Nonetheless, individuals can sometimes fall asleep without preparation, even under undesirable circumstances. These abrupt transitions into sleep can have severe consequences, particularly in high-risk environments. Although progress has been made in identifying neuronal populations controlling sleep-wake states and mechanisms regulating cortical oscillations during sleep, little is known about the natural processes that govern the pre-sleep phase, under baseline conditions and following sleep loss. Here, we examine factors regulating pre-sleep behaviors using environmental and behavioral manipulations, video recordings, machine-learning-based tracking, and EEG-EMG analysis in freely-behaving mice. We focus on nest-building-a key pre-sleep behavior-and assess its modulation by time of day and sleep deprivation. We find that mice are highly motivated to build nests during the light phase but show reduced motivation during most of the dark phase. Sleep deprivation significantly suppresses pre-sleep nest-building and promotes the direct initiation of sleep. Varying amounts of sleep deprivation, from 2-6 hours, uniformly suppress nest-building. This suppression is not due to stress, as mice exposed to acute restraint stress engage robustly in nest-building. Our findings provide insight into processes regulating the transition from wakefulness to sleep. Understanding pre-sleep regulation has important implications for treating sleep-onset difficulties-prevalent in insomnia and predictive of cognitive decline-and for mitigating risks associated with uncontrolled sleep onset in high-stakes situations.
在睡眠前的这段时间里，人类和其他动物会表现出一系列刻板行为，包括与卫生相关的活动以及准备睡觉的地方。有证据表明，这个睡眠前阶段对入睡和睡眠质量有积极作用。然而，个体有时即使在不理想的情况下也能毫无准备地入睡。这些突然进入睡眠的情况可能会产生严重后果，尤其是在高风险环境中。尽管在识别控制睡眠 - 觉醒状态的神经元群体以及调节睡眠期间皮层振荡的机制方面已经取得了进展，但对于在基线条件下以及睡眠剥夺后控制睡眠前阶段的自然过程却知之甚少。在这里，我们在自由活动的小鼠中使用环境和行为操纵、视频记录、基于机器学习的跟踪以及脑电图 - 肌电图分析来研究调节睡眠前行为的因素。我们专注于筑巢——一种关键的睡眠前行为——并评估其受一天中的时间和睡眠剥夺的调节情况。我们发现，小鼠在白天有很强的筑巢动机，但在大部分夜间则表现出较低的动机。睡眠剥夺会显著抑制睡眠前的筑巢行为，并促进直接入睡。从2到6小时不等的不同程度的睡眠剥夺都会一致地抑制筑巢行为。这种抑制并非由压力导致，因为暴露于急性束缚应激的小鼠仍会积极地筑巢。我们的研究结果为调节从清醒到睡眠的转变过程提供了见解。了解睡眠前调节对于治疗入睡困难（在失眠中普遍存在且可预测认知能力下降）以及减轻高风险情况下与不受控制的入睡相关的风险具有重要意义。
