Sleep loss overrides sleep-preparatory behavior to promote sleep

Abstract

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. STATEMENT OF SIGNIFICANCEPrior to sleep, animals-including humans-engage in stereotyped behaviors such as preparing a sleep space, thought to facilitate sleep initiation and quality. However, sleep can occur abruptly without preparation, posing serious risks, especially in high-stakes environments. Despite progress in understanding sleep/wake circuitry, the regulation of pre-sleep behaviors remains poorly understood. Here, we used multiple techniques in mice to examine nest-building, a key pre-sleep behavior. We found that mice are more motivated to build nests during the light phase, but this behavior is strongly suppressed by sleep loss and is not affected by acute stress. These findings highlight pre-sleep behaviors as an active, regulated component of sleep onset, with implications for understanding and treating sleep initiation difficulties.