BioTechniques News
Beatrice Bowlby
We all know the feeling: bleary eyes, irrepressible yawns – both unmistakable signs the land of nod is calling. But what is going on in our brains as we’re struck by a wave of sleepiness? A new preclinical study sheds some light on the science of sleep drive.
Scientists at the University of Basel (Switzerland), in collaboration with researchers from Beth Israel Deaconess Medical Center (MA, USA) and Auburn University (AL, USA), have identified neurons in the brains of mice that are activated during periods of prolonged wakefulness and are essential for inducing tiredness. The breakthrough represents “an important missing piece of the puzzle in understanding why we become sleepy,” lead author Alex Schier (University of Basel) divulged.
Sleep drive – aka the body’s need for sleep – increases with time spent awake, until it becomes impossible to ignore. This homeostatic regulation of sleep is intrinsic to our survival, and yet we know relatively little about it. Although previous studies in humans and animals have identified genetic loci that regulate sleep amount and electrical activity that occurs in the brain during slumber, the underlying neural mechanisms that generate the powerful urge to snooze remain a mystery.
To try and gain a better understanding of this complex interplay between sleep and wakefulness, the team performed whole-brain activity mapping, targeted neuronal manipulations and electrophysiology in mouse models to pinpoint specific neuronal populations that regulate sleep drive.
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First, they compared brain activation patterns in mice during normal sleep–wake cycles, sleep deprivation and recovery sleep. The rodents were euthanized for whole-brain FOS immunostaining – Fos labels activated neurons that control homeostatic behaviors – as well as tissue clearing and light-sheet imaging, which revealed that distinct areas of the brain are active during prolonged wakefulness. Specifically, the anterior medial preoptic area and median raphe were identified as regions that likely encode sleep deprivation.
To selectively target cells within these areas that become activated thanks to lack of sleep, the researchers used a mouse line with inducible Cre recombinase knocked in at the Fos locus. Cre induction towards the end of a 6-hour deprivation period identified threefold more cells than it did during recovery. In subsequent experiments, activating these sleep-deprivation-responsive cells resulted in increased sleep duration and intensity, while inhibiting them reduced sleep.
The team then sought to identify deprivation-sensitive cells within the median raphe. Via co-localization experiments, they recognized two neuronal populations that influence sleep drive: serotonergic and GABAergic neurons, whose excitability increased the longer the animals were kept awake. Finally, they demonstrated that co-activation of serotonergic and GABAergic neurons promoted sleep, whereas co-inhibition of the neurons reduced shut eye by almost 70%.
Together, the findings highlight neuronal populations that are crucial to sleep drive, opening doors in sleep research that could inspire new therapeutic approaches for the treatment of sleep disorders.
“Future studies could reveal how these neurons interact with the rest of the brain, and how sleep drive is generated at the molecular level,” surmised William Joo (University of Basel), first author of the study. “Our ability to stably transform sleep behavior also allows us to explore adaptations to long-term sleep loss – this may eventually reveal ways to confer resilience to sleep deprivation and other physiological challenges.”
The post Why do we get sleepy? Uncovering the science of sleep drive appeared first on BioTechniques.
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