Why do we sleep? A new paper from Hertford neuroscientists
2 August 2021
Published today in Nature Neuroscience, a study led by Hertford DPhil candidate Lukas Krone opens new and exciting perspectives on the fundamental question underpinning sleep science: why do we sleep?
Led by Lukas at the Department of Physiology, Anatomy and Genetics, the study was a collaboration between the laboratories of Hertford medicine fellow Dr Vlad Vyazovskiy and Professor Zoltán Molnár of St John’s College, who completed his own DPhil at Hertford in 1994. The main motivation behind the research was to further our understanding of sleep-wake control, a theory which has been in development for over a century, by addressing the role played by the cerebral cortex in regulating sleep.
The work of Constantin von Economo, and later Clifford Saper, established the theory of a localised ‘sleep centre’ in the brain and a potential ‘sleep switch’ which has been the subject of much research over the last few decades. However, many of these previous studies use activity in the cerebral cortex merely as an indicator of sleep-wake state. The authors of the current paper have instead used this activity – cortical oscillations – as a way to understand homeostatic regulation, the central functional property of sleep. Sleep homeostasis refers to the still enigmatic process through which the brain adjusts the depth and duration of sleep to the need for sleep, which builds up during wakefulness.
The Nature Neuroscience study monitored brain activity in laboratory mice to investigate the role of the cortex in sleep at three distinct levels: the local dynamics of sleep oscillations, global architecture of sleep-wake states and sleep homeostasis. Although mice have much smaller brains than humans, both species show fundamental similarities in brain anatomy and the mechanisms of sleep regulation. In mammals, the cerebral cortex is a layered structure and, by working with mice, the researchers were able to use revolutionary techniques to selectively silence a subset of neurons in one particular layer. While the mice were unlikely to have noticed the difference, this adaptation led to them staying awake for three hours more every day. To put this into perspective, an average mouse lives for two years, so those in the study gained three full months of wake time over their lifespan; in humans this would equate to about ten years.
Normally, mice (and humans!) get tired the longer they stay awake and this is reflected in deeper or ‘more intense’ sleep afterwards. Perhaps not unexpectedly, this is not what was observed in the study: when the mice went to sleep after staying awake for longer their sleep was not much deeper than it is normally. Working with the Oxford Sleep and Circadian Neuroscience Institute (SCNi), the authors also measured the parameters of their daily rhythms, which appeared to be completely normal. This is an important finding, as it suggests that the phenotype observed arose from the change in core sleep mechanisms rather than being an altered response to external cues such as light.
Altogether, the study offers new perspectives for understanding the neural substrates of sleep-wake control. The prevailing model is that sleep-wake states are controlled by structures deep in the brain only. The new paper demonstrates that this is not the case and, contrary to the predominant view, that the cortex plays a much greater role than has previously been appreciated. This work provides important theoretical basis for the development of novel therapies and sleep modulation technologies, aimed to improve or enhance sleep when it is disrupted. FIND OUT MORE & READ THE PAPER HERE