Finding may provide new insights into the neurological basis of ADHD, learning deficits, and more
Scientists at the California Institute of Technology (Caltech) have uncovered evidence of a primitive emotion-like behavior in the fruit fly, Drosophila melanogaster.
Their findings, which may be relevant to the relationship between the neurotransmitter dopamine and attention deficit hyperactivity disorder (ADHD), are described in the December issue of the journal Neuron.
The Drosophila brain contains only about 20,000 neurons and has long been considered a powerful system with which to study the genetic basis of behaviors such as learning and courtship, as well as memory and circadian rhythms. What hasn't been clear is whether the Drosophila brain also could be used to study the genetic basis of "emotional" behaviors.
"Such studies are important," says David Anderson, Caltech's Seymour Benzer Professor of Biology and a Howard Hughes Medical Institute investigator, "because it's believed that abnormalities in these types of behaviors may underlie many psychiatric disorders."
Most of the genes found in the fruit fly-more accurately referred to as the vinegar fly-are found in humans as well, including those neurons that produce brain chemicals like dopamine and serotonin, which have been implicated in psychiatric disorders.
In their Neuron paper, the Caltech team-led by postdoctoral fellow Tim Lebestky-found that a series of brief but brisk air puffs, delivered in rapid succession, caused flies to run around their test chamber in what Anderson calls a "frantic manner." This behavior persisted for several minutes after the last of the puffs.
"Even after the flies had 'calmed down,'" he adds, "they remained hypersensitive to a single air puff."
To quantify the flies' behavior, Anderson's group collaborated with Pietro Perona, the Allen E. Puckett Professor of Electrical Engineering at Caltech. Together with his students, Perona developed an automated machine-vision-based system to track the movement of the flies, and derived a simple mathematical model to fit the movement data and to extract metrics that described various aspects of the flies' responses under different conditions.
The researchers used this test to search for flies with an abnormally exaggerated hyperactivity response; genetic studies of these flies revealed that a mutation in a dopamine receptor (a mutation that eliminates the receptor) produced the aberrant behavior. Flies with this dopamine-receptor mutation were hypersensitive to the air puffs, and took much longer to calm down than did "normal" flies without the mutation.
What is surprising about this result, notes Lebestky, "is that previous studies in both flies and vertebrates had suggested that dopamine promotes activity, but our experiments uncovered a function of dopamine in the opposite direction." Because removing the receptor causes hypersensitivity to the air puffs, these results "suggested that dopamine actively inhibits the hyperactivity response," Lebestky says.
This observation suggested a possible link to ADHD, a behavioral disorder characterized by impulsivity, hyperactivity, and short attention span. Humans with the disorder often take drugs, such as Ritalin, that increase levels of brain dopamine in order to reduce hyperactivity.
The ways the mutant flies respond to the air puffs is, moreover, "reminiscent of the way in which individuals with ADHD display hypersensitivity to environmental stimuli and are more easily aroused by such influences," says Anderson. Importantly, ADHD has been genetically linked to abnormalities of the dopamine system in humans, further strengthening the analogy between the mutant flies and this psychiatric disorder.