Flies Provide Insight Into Human Sleep

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Research on fruit flies by the University of Wisconsin School of Medicine and Public Health provides insight into human sleepMADISON - If you give them caffeine, they're buzzing. If you give them antihistamines, they're drowsy, and if you deprive them of a decent night's sleep, they get stupid and make mistakes.

Flies are not the stuff dreams are made of, but their sleep patterns are surprisingly like our own.

And now they're pointing towards a way to help humans "power nap" to make up for lost sleep.

Fruit flies have been used in many kinds of medical research for years, but the joint lab of UW School of Medicine and Public Health psychiatrists Chiara Cirelli and Giulio Tononi was one of the first in the world to use them as a model for human sleep.

The flies have a short lifespan and lay eggs every day, and a lot is already known about their genetics.

But how do you prove that flies sleep?

It's not as easy to find out as you might imagine. At first, the researchers simply observed the flies, noting that the insects had a quiet period of about 10 hours when they didn't respond to stimuli and were difficult to arouse. It looked like sleep, but some researchers were still skeptical.
Then back in 2000, the scientists did a one-time experiment to prove that dozing fruit flies have brain waves similar to those of sleeping mammals. First, the tiny fly was immobilized on a peg, then a small electrode was inserted into the central part of the fly's even tinier brain. The EEG, or electroencephalogram, showed that the brain activity had different patterns during sleeping and waking.

"We use the probes all the time in mammals to study sleep, but in flies it was a one-time experiment to prove the principle," Cirelli explains.

Today, about 10 laboratories worldwide use Drosophila melanogaster, or fruit flies, to study sleep.
Much of the equipment to do it was invented at UW. The "fly agitator" holds 10 plates, each containing 32 drowsy flies, and a robot arm shakes them occasionally to keep the flies awake. Researchers have found that like humans, flies experience "sleep rebound"; they sleep longer than normal following missed sleep. They also perform more poorly on tests, such as learning to avoid a hot, uncomfortable area, when they are tired.

Another device allows scientists to track fly activity by counting each time a fly breaks a beam of light, signaling that the fly is awake.

The lab has spent years looking for fly DNA mutations that affect sleep. They screened more than 15,000 mutant lines of flies, and found about 10 with mutations that allowed the flies to stay awake much longer than normal flies.

And in 2005, the Wisconsin researchers discovered a gene that controls how long the flies stay asleep. "Mini-sleeper" flies with the mutated "Shaker" gene got by nicely on two hours of sleep, compared with regular flies who sleep up to 12 hours at a time. The gene controls the flow of potassium into cells, which, in the brain, affects electrical activity in neurons. Humans have several "Shaker"-like genes. (The gene, which affects many other cellular functions, got its name because flies with it shake when they recover from anesthesia.)

This year, fruit-fly researchers at the University of Pennsylvania found a second gene, called "Sleepless," that also keeps flies awake when mutated. It may work with "Shaker" to open and close the potassium channels.

Cirelli and Tononi's "Shaker" gene research was funded by the Defense Advanced Research Projects Agency (DARPA) because the military is interested in ways of fighting sleep deprivation among its troops. (Their current funding comes from the National Institutes of Health.)

So far, a drug that would allow people to stay up all night without impairment hasn't emerged, Cirelli says, but different help for tired humans is possible.

"It may be possible to enhance the potassium channels to get a deeper, more efficient sleep," she says. "You could create a power nap."

So if someday you can take a two-hour nap to replace a missed night's sleep, you can thank a fruit fly for its tireless contribution to science.

Date Published: 10/27/2008

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