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Bruce O'Hara: Why Do We Need to Sleep?

by Jeff Worley

Dreamland.

We spend a third of our lives in the state of relative unconsciousness, and we have no idea why," says Bruce O'Hara, a UK associate professor of biology. "How is sleep regulated? What causes it? If it's just a matter of physical tiredness, why can't you just sit down, rest and be restored?" For over 20 years, these questions have intrigued O'Hara, who earned a Ph.D. in human genetics from Johns Hopkins University in 1988. His research focus there was on how human genetics affects the brain and behavior.

"Something about the brain is presumably different from the rest of your body. If you sit down, your heart rate slows and muscles relax, but the brain is still just as active," says O'Hara, who came to UK from Stanford University last August, attracted by a tenure-track position here and the promise of support to start up a lab in the Morgan Biological Sciences Building.

"Sleep doesn't make your heart rate drop much more than if you're just sitting and relaxing, so going to sleep doesn't help your heart. There's a sharp consensus now that the rest of your body doesn't need sleep; just the brain. Your heart, muscle, bones, liver, and kidneys don't really care if you're conscious or not."

It's likely, O'Hara adds, that sleep has more than one function, since virtually all birds and mammals have two very different kinds of sleep—Rapid-Eye-Movement (REM) sleep, a mentally active period during which most dreaming occurs, and non-REM sleep, the more restorative phase of sleep during which the brain is relatively quiescent.

Understanding sleep is important, O'Hara says, because sleep is of great medical and societal consequence. Sleep disturbances afflict approximately 75 million people in the United States alone. The most common sleep disorders include insomnia, sleep apnea and restless leg syndrome. All three of these disorders, he says, increase substantially with age.

Insufficient sleep is most clearly manifested in brain performance, O'Hara says, and can be downright dangerous. Sleepiness, for example, is the single largest factor in industrial accidents. Also, O'Hara cites a study in which subjects got five hours' sleep five nights in a row and then were asked to take a driving test. The sleep deprivation resulted in driving skills equal to someone with a blood alcohol level well over the legal driving limit.

"Clearly, something about the brain requires sleep. And in our view, genetic approaches offer the best hope of understanding this sleep need," says O'Hara, who worked for 12 years in Stanford's Center for Sleep and Circadian Neurobiology. (Circadian: approximately 24-hour rhythms).

In their search for "sleep genes," O'Hara and his team are using strains of mice that differ in their sleep behaviors. "By crossing strains of long-sleep mice with short-sleep mice, we can examine sleep in the offspring and look for alleles of genes for long or short sleep," he says.

Alleles, O'Hara explains, are different forms of genes, genes that encode slight differences. "Alleles are what cause someone to have blue eyes rather than brown eyes, or type O blood instead of another type. They are what make us different genetically."

But back to the mice. How do you measure sleep in mice?

One problem with analyzing sleep patterns of mice, O'Hara explains, is the difficulty of performing EEG analysis on them. So his team is working on an easier way to monitor sleep and wakefulness accurately, using a piezoelectric surface—an electric grid that serves as an extremely sensitive motion detector.

During sleep, essentially the only signal is from the movement of the chest and abdomen that accompanies respiration, O'Hara explains. Breathing is quite regular during non-REM sleep and less regular during REM sleep. In a waking state, even when resting, mice make a variety of non-respiratory movements—walking, rearing, grooming, postural adjustments and so forth—that allow the researchers to distinguish easily between wakefulness and sleep.

"This piezoelectric system will allow us to examine many more offspring from genetic crosses, examine more genetically altered mice, and to find alleles of genes that influence sleep.

"Until five or six years ago people only talked about sleep in birds and mammals," O'Hara says, "but there's a growing consensus that all animals sleep, including insects."

"If we accept the premise that all animals sleep, then it looks like there's something special about neurons, about basic energy requirements. Neurons are among the cells that have highest energy requirements. Our brain, 1 or 2% of our total bodily weight, uses up 20% of our energy; so the brain is the most energy-demanding organ we have," O'Hara explains. He concludes that energy usage is one very possible function of sleep. Neurons require this loss of consciousness to slow down just enough so they can replenish themselves for normal functioning. "It's hard to get solid data to support that, but no data I know of refutes the idea."

O'Hara, who has published over 40 articles and given dozens of presentations on his sleep-related research, says that he gets one commonly asked question wherever he goes: Why do some people get by just fine on four to five hours of sleep and other people need eight or more?

"I'm very interested in this question really," O'Hara admits. "A lot of it is probably genetic, like for any trait." In dealing with the question, he says you have to be very careful with claims people make. "Some people think they sleep very little, but if you measure their sleep, they actually sleep more than they think they do—or claim to. Ninety percent of the population needs at least six hours' sleep a night, or their performance drops dramatically over successive days," he adds.