Sleep deprivation can be dangerous, but it’s difficult to measure.Credit: Getty
How does the brain know when it’s time to wake up? Researchers have identified1 a chemical signal that serves as a timer in the mouse brain, logging both the length of a single sleep session and the number of interruptions and predicting exactly how likely an animal is to wake up at any given moment.
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This signal could offer a new way to measure ‘sleep debt’, or accumulated sleep loss. Such a biomarker could one day lead to methods for checking whether someone is sleep-deprived, says Ketema Paul, a neuroscientist at the University of California, Los Angeles, who was not involved in the research.
“We really don’t have what a lot of people call the sobriety test for sleep,” Paul says, adding that such a test could be useful to ensure that people in high-stakes occupations, such as driving trucks or working in a hospital emergency room, are able to remain alert. “The negative effects of sleep loss can have serious negative consequences.”
The work was posted on the bioRxiv preprint server and has not yet been peer reviewed.
Missing marker
Previous sleep research has focused mostly on the brain circuitry that snaps people awake in seconds or on how sleep debt accrues after days of bad sleep. But the intermediate time scale — how the brain keeps track of the minutes or hours spent in a single continuous session of sleep — has remained a mystery.
To investigate, Yao Chen, a neuroscientist at Washington University in St. Louis, Missouri, and her team searched for molecular signals that shift gradually during a sleep session. The researchers used a specialized fluorescent sensor in the brains of mice to watch, in real-time, the effects of protein kinase A, or PKA — an enzyme also found in humans and previously linked to wakefulness2. This enzyme adds chemical ‘tags’ to proteins on the surface of brain cells.
They discovered that the presence of those tags followed a distinct and predictable rhythm: when the mice were awake, the level of protein tagging stayed high and steady. But as soon as the mice drifted off, the degree of protein tagging began a slow, continuous decline that lasted for the entire sleep session. Whenever the mice experienced a microarousal, or a brief interruption in their sleep, the PKA-related signal spiked upwards before dropping again.
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That means that the tagging simultaneously tallies total sleep duration and the frequency of interruptions, Chen says. Because the PKA signal accounts for these restless moments, monitoring it can more accurately predict the moment-to-moment probability that the mouse is about to wake up than tracking how long the animal has been asleep, the researchers found.
The degree of tagging doesn’t act as an alarm clock that triggers the exact second of waking, which could be caused by a sudden noise, says Chen. Instead it reflects a growing physiological readiness to wake, she says.
