After more than a decade, one researcher and his colleagues have finally uncovered the mechanism behind how an animal’s biological clock wakes it up and puts it to sleep.
The findings of the study, published in Cell, could eventually lead to new drug targets for treating disorders related to body clock problems, such as jet lag.
Lead author Matthieu Flourakis and his colleagues discovered that the mechanism for sleep-wake cycle control was the same in both fruit flies and mice.
“What is amazing is finding the same mechanism for sleep-wake cycle control in an insect and a mammal,” he says. “Mice are nocturnal, and flies are diurnal, or active during the day, but their sleep-wake cycles are controlled in the same way.”
The journey to this discovery began 15 years ago when senior author Dr. Ravi Allada, a neuroscientist at Northwestern University in Evanston, IL, examined a mutant fruit fly.
“Our starting point for this research was mutant flies missing a sodium channel who walked in a halting manner and had poor circadian rhythms,” Dr. Allada explains. “It took a long time, but we were able to pull everything – genomics, genetics, behavior studies and electrical measurements of neuron activity – together in this paper, in a study of two species.”
The need for sleep is produced by a body system known as sleep/wake homeostasis. This system also helps people to stay asleep during the night to make up for the number of hours spent awake during the day.
Cells in the brain known as circadian neurons are responsible for the sleep-wake cycle. In the new study, the researchers discovered that a simple oscillation mechanism in these neurons drove waking and sleeping.
At the start of the study, Flourakis questioned whether the mutant flies’ circadian neurons changed throughout the course of the day. The team found that the neurons were very active in the morning but did very little in the evening. Their next step was to discover why.
The researchers then found that high sodium channel activity early in the day led to the circadian neurons firing more, waking the animal up. In contrast, high potassium channel activity later in the day made the neurons less active, leading the animal to sleep.
As this mechanism has two separate “pedals,” the researchers refer to it as a “bicycle mechanism.” These two pedals oscillate up and down across a period of 24 hours, governing when the creature’s body clock tells it to wake up or go to sleep.
Once the bicycle mechanism had been established, the researchers wanted to find out whether it was present in an animal more similar to humans than the fruit fly. To test this, they examined the suprachiasmatic nucleus of the mouse – an area of the brain consisting of 20,000 neurons that controls its body clock.
They were surprised to discover that the sodium and potassium currents were both active in the mouse brain in the same way. Dr. Allada describes the implications of the discovery in mice:
“This suggests the underlying mechanism controlling our sleep-wake cycle is ancient. 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 team believes that if they develop a fuller understanding of this bicycle mechanism, it is conceivable that in the future, people may be able to alter their body clocks to suit their situation – a development that would be welcome among the thousands who work shift patterns outside traditional working hours.
At the start of the year, Medical News Today ran a Spotlight feature that examined the impact of shift work – working unconventional hours, including night shifts – on health.