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NEUROBIOLOGY The Fruit Fly Fight ClubFly Model Facilitates Research on Aggression The fight in the Goldenson building began as these fights often do. The two male rookies circled each other warily. Making the first move, the yellow-clad youth approached and charged his competitor. The one wearing the white spot bristled in defense, seized the offensive, and lunged in retaliation. Wings flared. White soon chased off yellow, ending the fight and establishing dominance in mere seconds.
Hit 'em with your best shot. Rarely seen, fruit fly fights can reach a high level of aggression when the animals box (top left), wrestle and tussle. Mid-level aggressive moves are more common (top middle), such as the close chase by the winning fly on the right and the defensive wing threat by the loser on the left. Most fights are decided by low-level aggressive moves, such as a wings-up display (top right), charging, or a limb lifted to the side. The research team of undergraduates Selby Chen, Ann Lee, Nina Bowens (not pictured), and professor Ed Kravitz has scored dozens of fights between fruit flies, hoping to gain more insight into genes underlying aggressive behavior. Images of flies courtesy of Ed Kravitz. Photo by Steve Gilbert It all happened so fast, Harvard University undergraduate researcher Selby Chen needed to slow the instant replay down to frame-by-frame action to properly score the fight. As in this bout, winners and losers usually are decided by a series of mildly aggressive moves. Occasionally, a fight can escalate to boxing or all-out locked-limb wrestling and tussling. Without the catchy superlatives or clever nicknames usually associated with the sport of boxing, this fight club for fruit flies has been going on for more than a year in the third-floor lab of Edward Kravitz, the George Packer Berry professor of neurobiology at HMS. The mild-mannered Kravitz has promoted more fights than Don King. For 20 years, pair after pair of young lobsters have challenged, darted, and wrestled their way to dominance or defeat. Then last spring, Kravitz's research team began staging matches involving the common laboratory fruit fly, Drosophila melanogaster. Building a BaselineWhat is lacking in hyperbolic buildup is made up by the rigorous ongoing analysis of the sometimes amusing fights replayed on iMovie. The researchers are collecting baseline data to calculate statistically what constitutes a "normal" fight. Based on preliminary analysis, the fights and subsequent behaviors seem to follow rules set by a combination of genetics and fight outcomes. Kravitz wants to use the fighting fruit fly model system to explore the neurobiology of aggression.In this case, normal does not mean natural chance encounters. The fights take place between pairs of 3-day-old males, raised in isolation and then trapped together in a small, temperature-controlled, clear plastic and glass chamber. There a headless pregnant fruit fly perches on a bottle cap-sized food cup. (Females with heads intact tend to fly away from the fight.) The female lures the males to the cup, where the flies instinctively wage a turf battle. On one side of the chamber is the close-up lens of a digital camera perched on a tripod. It is easy to see human parallels to Kravitz's fighting animal models, such as working on a project with an antagonistic colleague. "In the wild, the animals might run away from each other, but we don't let them run away," Kravitz said. "If you can't escape from the situation--and one can think of lots of times with people when you can't escape--then a winner mentality and loser mentality can develop." So far, the researchers have videotaped 75 fights between flies involving 2,000 rounds. Earlier this month at the Society for Neuroscience meeting in San Diego, Kravitz presented a poster showing the preliminary analysis. Fights can be decided after encounters as short as a few seconds or as long as 1.5 minutes. In a half-hour fight, the researchers see anywhere from three to 63 encounters, with a mean of 27. The average time is 11 seconds. The first male to reach the food surface usually picks the fight. The researchers score rounds at three intensity levels (see photos). High-level encounters last longer (26 seconds) than mid- and low-level rounds (12 and 6 seconds, respectively). After a high-intensity round knocks the loser off the fruit cup, the defeated fly takes about twice as long to engage in another encounter (52 seconds) as it takes after a low-intensity encounter (28 seconds). The difference suggests a long-term component to the fighting behavior. The Fight CircuitThis long-term component may reflect changes in gene expression in the brain. Two decades of researching the conveniently large neurons in the lobster has helped Kravitz define some of the neurotransmitters important in aggressive behavior, and to identify circuitry important in the winner and loser roles adopted by the lobsters (see Focus, May 24, 1996)."We don't know how, but the business of being beaten clearly has a dramatic effect on the life of a lobster," Kravitz said. "After a fight, one becomes dominant, the other subordinate. The dominant animal advances all the time, and the subordinate runs away and won't fight. After a half hour of fighting in lobsters, animals can remember for up to a week who is a winner and who is a loser without having any fights in between and after being separated from each other." Kravitz's group has found that two important neurotransmitters for aggression in lobsters are the amines, serotonin and octopamine (the lobster equivalent of norepinephrine in the human nervous system). The amines influence the animals' post-fight postures in opposite ways. A serotonin injection causes animals to stand tall and assume a dominant stance while octopamine causes animals to assume a lowered, subordinate-looking stance. Also, raising levels of serotonin in losing lobsters enhances their willingness to fight again. "Nerve cells containing these substances are not involved in the point-to-point connectivity characteristic of most nerve cells," Kravitz said. "Instead, they are specialized to influence many parts of the central and peripheral nervous system governing particular aspects of an animals' behavior. If amine-containing nerve cells function in similar ways in humans, that could help to explain their involvement in so many diverse functions." Fruit flies now offer Kravitz and his colleagues an opportunity to use new genetic research tools to explore changes in gene expression related to changes in social experience and to identify pathways important in animals' aggressive behavior. In the next series of fights, Kravitz envisions pairing normal flies with flies carrying mutations expressed only in a certain temperature range and in a small number of nerve cells in the brain. The idea is to let a pair of flies establish a hierarchical relationship at one temperature and then turn up the heat to study how particular mutations alter winner and loser activity. "Aggression is a serious problem in society, but even after studies of lots of animal models for many years, we don't know a lot about the biological basis of aggression," Kravitz said. "We know that some chemicals like serotonin are very important, but beyond that, much remains to be discovered." If nothing else, it is a field of study that will never be dull. --Carol Cruzan Morton |
