What Good Is Sleep? New Lessons from the Fruit Fly

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If fruit flies could talk, that's probably how they would call bouts in the Fruit Fly Fight Club in Edward Kravitz's lab at Harvard University. Kravitz, a neurobiologist, has been pitting fruit flies against one another for decades and has painstakingly videotaped thousands of hours of fruit-fly fistfights (yes, they get up on their hind legs and brawl) in an effort to better understand aggression — not only in the insects but possibly in humans as well. (See the top 10 scientific discoveries of 2008.)

Kravitz is hardly the only scientist so taken with the red-eyed bugs. While the antics of Drosophila melanogaster, as the fruit fly is known in scientific circles, may seem irrelevant at first blush, they are anything but. Remember, it was the fruit fly, which has been used in experiments of heredity for some 100 years and whose genome was fully decoded in 2000, that first educated us far more complex human beings about the way our genes work. In essence, it was on the tiny back of the fruit fly that scientists launched a genetic revolution. (See pictures of Charles Darwin's legacy.)

And lately there has been a lot of activity in the fruit-fly world. Along with information about social behaviors like aggression and fighting, fruit-fly research is beginning to yield insights into other complex behaviors, such as sleep. In two papers published today in Science, researchers find clues to the long-standing mystery of why humans need sleep, by studying the way Drosophila catches its Z's.

In the first study, Paul Shaw at Washington University in St. Louis monitored the relationship between brain activity and sleep patterns in a group of fruit flies and isolated three key genes responsible for dictating how much sleep flies got in certain situations and when. Under normal conditions, flies doze off, even during the day, after engaging in intense social activities, including courtship, acclimating to a new environment and fighting over mates and territory. But Shaw found that when flies were genetically bred to be missing the three genes — colorfully named rutabaga, period and blistered — that, among other functions, help regulate sleep, they failed to fall asleep after busy episodes of social activity.

Such alertness may not seem like a bad thing, except that in a second paper in the same issue of Science, Giulio Tononi at the University of Wisconsin found that sleep appears to function as a critical shutoff valve for the fruit-fly brain. After a period of sleep, the volume of connections between nerve cells in the brain decreased, a condition that Tononi theorizes offsets the wakeful brain's activity. During waking hours, the brain keeps adding new information about its environment, forming new circuits and new connections in an ever thickening neural network. But even the fruit-fly brain has its limits and, like any computer, needs a fail-safe shutdown mode as it gets close to overload. That's where sleep comes in. (See pictures of how animals sleep.)

Tononi and a growing number of other scientists believe that sleep — not just in flies but also in higher-order mammals — may perform such a pressure-releasing role. During sleep, researchers theorize, the brain actively prunes the neural network laid out during waking hours, trimming away weaker connections that haven't been used in a while or weren't strong enough to begin with. The stronger connections are believed to be filed during sleep into long-term memory, where they can be accessed again and again as needed. All this nocturnal tidying creates room for new connections to be formed when the brain wakes again. "If this didn't happen, theoretically, over time, the brain would reach capacity and be unable to learn or remember new things," says Shaw. "After a night's sleep, the next morning the brain wakes up and is ready to go, ready to acquire new information."

That makes sense for a human. But exactly how much new information does a fruit fly acquire in a day? How complex could Drosophila's world be that it actually needs shut-eye to recharge its brain? You'd be surprised. For a fly, its brief, two-month life can only be about mating and eating — or eating and mating, depending on whether mates or food are in shorter supply — but these activities involve complex social interactions that, frankly, can be exhausting.

Take mating, for instance. When females are scarce, males, not surprisingly, have to fight for the right to mate. Females, on the other hand, are on the hunt for not just any mate but one that can provide food for both her and the clutch of eggs she will lay. (Females, in the ultimate bow to efficiency, tend to lay their eggs on a food source, thus ensuring their offspring have a ready supply of nutrition.) So for males, securing a territory with a food patch is critical to attracting the attentions of a female. (See the top 10 medical breakthroughs of 2008.)

Kravitz and his research team have been documenting, on video, exactly how far fruit flies are willing to go for their prize. In this fight club, the arena is a small dish, in the center of which is either a patch of food or the head of a female. (If she weren't decapitated, she wouldn't stay put, says Kravitz; and the males, being male, don't seem to care that she's not that lively.) Based on hours of footage, Kravitz says that male flies tend to use specific combat skills such as rearing up on their hind legs and lunging at their opponents when fighting over a mate. Females fighting over food, meanwhile, tend to use head-butting and shoving tactics.

That finding in and of itself isn't very revolutionary, but Kravitz was also able to link Drosophila's sex-specific behaviors to genes. When male flies were bred with the female version of the fighting gene, they tended to act like females, favoring head butts and shoves over the more aggressive lunges. Same went for the female flies bred with the male version of the gene — they acted more like male flies, often even attempting to mate with other females.

The next step, obviously, would be to see if these same genes appear in mammals' or even the human genome. Chances are good: the fruit-fly genome is made up of 14,000 genes, while the human genome contains 20,000. Much of the molecular machinery underlying species as varied as flies and humans might therefore be conserved, which is why the lowly fruit fly makes a worthy model for understanding human beings, even for such complex behaviors as aggression.

"Trying to understand the relationship between a set of neurons and its behavioral output is going to be difficult unless we are able to look at an organism that is simple enough where we can use our genetic tools," says Herman Dierick, a human- and molecular-genetics expert at Baylor College of Medicine. "That's where the usefulness of flies lies. Fruit flies have made such a difference in biology over the past century." And if the recent papers are any indication, these fascinating, high-spirited and surprisingly engaging little bugs will continue to do so for a long time to come.

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