We know that a tiny region in the hypothalamus of the brain is responsible for regulating one's "biological clock" through both neuronal and hormonal activity. The genetic basis for the circadian rhythm – roughly 24-hour cycles of physiological processes – has been well studied across a range of species, from bacteria to animals, but until now the mechanism determining the timing of sleep-wake cycles remained unknown.
When looking at this region in the brain of fruit flies, researchers discovered that an increase in sodium levels in the circadian neurons during the day “turned them on” (causing wakefulness), while high potassium levels at night appeared to turn them off (allowing for sleep). What’s more, to their surprise they found that this same mechanism regulated the sleep-wake cycle in mice too.
“This suggests the underlying mechanism controlling our sleep-wake cycle is ancient,” explains Dr. Ravi Allada, professor of neurobiology at Northwestern University and senior author of the study published this week in the journal Cell. “This oscillation mechanism appears to be conserved across several hundred million years of evolution. And if it's in the mouse, it is likely in humans, too.”
The scientists originally wanted to know if the circadian neurons, in a region known technically as the suprachiasmatic nucleus, changed their activity over a period of 24 hours. And indeed, they found their activity to be higher during the day than at night. The next step was to investigate what was causing this difference in activity, and it was this work that led them to discover the changes in sodium and potassium levels.
The researchers describe this system as similar to “a bicycle,” in that the two pedals go up and down during a 24-hour cycle. When the sodium levels are up, the circadian neurons fire more, awakening the animal. When the potassium levels then rise, the neurons quiet down, allowing the animal to sleep at night. But this wasn’t the only aspect of their work that astonished them.
“What is amazing is finding the same mechanism for sleep-wake cycle control in an insect and a mammal,” said Matthieu Flourakis, who led the study. “Mice are nocturnal, and flies are diurnal, or active during the day, but their sleep-wake cycles are controlled in the same way.”
Their next step is to look further into what’s regulating this sleep-wake pathway. A better understanding of this mechanism could help with the development of new drug targets to help balance, and potentially even reset, the circadian clock in people suffering from jet lag or those employed in shift-work, for example.