Two aspects of sleep share a master

Ever pulled an all-nighter, then started to feel alert around 7 or 8 a.m.? That was your internal clock jolting you awake just when you wished you could crawl under the covers.

Researchers know that when and how long our bodies want to sleep are separate but interrelated behaviors. One system, the internal clock, controls the daily, or circadian, rhythm of when we have the urge to go to bed and wake up. The second, the so-called sleep-wake system, determines how much rest our bodies need.

At least one study already has shown that the internal clock also influences the duration of sleep, but scientists have been in the dark about how this influence plays out inside cells.

Reporting in the November Journal of Neuroscience, Fred W. Turek of Northwestern University in Evanston, Ill., and his colleagues offer what they say is the first evidence of a molecular link between the internal clock and the sleep-wake system.

They report that a mutation in one of the genes known to control when animals fall asleep not only throws off their bedtime, but also changes how long they slumber. Mice with a mutation in one of their two copies of the gene named Clock slept 1 hour less than their normal counterparts, while mice with mutations in both copies of Clock slept 2 hours less.

This means the protein that Clock encodes, until recently associated only with circadian rhythm, either directly controls the sleep-wake system or regulates other genes that do, Turek says. Clock could be a marker for the gene or genes that control the length of sleep, he adds.

The group’s results reinforce a 1993 report that the internal clock in monkeys has a physiological connection to sleep duration. In the earlier study, scientists found that damaging a part of the brain known to regulate circadian rhythms upsets the animals’ sleep patterns in both timing and—unexpectedly—duration.

“It was showing a connection between the neuroanatomical clock itself and sleep and wake,” says Allan I. Pack, director of the sleep research center at the University of Pennsylvania Medical Center in Philadelphia. By taking the link from the physiological level down to the molecular mechanism itself, Turek’s experiment goes a step further, Pack says.

It’s not surprising that Clock would do a job outside the realm of circadian rhythms, several scientists say. As Turek’s group points out, a 1999 study in Science found that a circadian rhythm gene that works with Clock helps control addictive responses to cocaine.

Clock and its family of genes “are expressed in many locations in the brain and elsewhere, and not all of these regions exhibit circadian rhythms,” says Gene D. Block, director of the National Science Foundation Center for Biological Timing in Charlottesville, Va.

“The fact that an identified gene has an effect on sleep duration [may] lead to a molecular understanding of sleep regulation,” Block continues. That, in turn, could produce treatments for jet-lag, insomnia, and other sleep disorders.

The mouse experiments might also suggest how to make drugs that let people in extraordinary circumstances, such as a military operation, get by on less sleep, Block says. That’s because the mutatnt mice sleep less than their normal counterparts without developing a socalled sleep debt.

“Many drugs can keep you awake,” he says, “but you must pay this back with additional sleep.”