Scientists at the California Institute of Technology (Caltech) are believed to have discovered evidence of a primitive emotion-like behavior in the fruit fly, Drosophila melanogaster. The findings of the study may perhaps be pertinent to the relationship between the neurotransmitter dopamine and attention deficit hyperactivity disorder (ADHD).
The Drosophila brain is known to contain only about 20,000 neurons. Moreover, it seems to have long been regarded as an influential system through which scientists study the genetic basis of behaviors such as learning and courtship, plus memory and circadian rhythms. However, what hasn’t been clear is whether the Drosophila brain also could be used to study the genetic basis of ‘emotional’ behaviors.
David Anderson, Caltech’s Seymour Benzer Professor of Biology and a Howard Hughes Medical Institute investigator said that, “Such studies are important 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 appear to have been seen in humans as well, together with those neurons that produce brain chemicals like dopamine and serotonin. Dopamine and serotonin appear to have been occupied in psychiatric disorders.
Lead author of the study and postdoctoral fellow Tim Lebestky along with his colleagues found that a series of short but brisk air puffs, delivered in rapid succession seemed to have caused flies to run around their test chamber. Anderson supposedly calls this test chamber a ‘frantic manner.’ Furthermore, this behavior was noted to have persisted for several minutes after the last of the puffs. Even after the flies had ‘calmed down’ they appeared to have remained hypersensitive to a single air puff.
In order to quantify the flies’ behavior, Anderson’s group appeared to have collaborated with Pietro Perona, the Allen E. Puckett Professor of Electrical Engineering at Caltech. Subsequently, they developed an automated machine-vision-based system to track the movement of the flies. Further, they seemed to have derived a simple mathematical model to fit the movement data. More so, they extracted metrics that explained various aspects of the flies’ responses under different conditions.
The authors made use of this test to investigate for flies with an abnormally exaggerated hyperactivity response. Genetic studies of these flies revealed that a mutation in a dopamine receptor seemed to have produced the abnormal behavior. Dopamine receptor is known to be a mutation that eliminates the receptor. Additionally, flies with this dopamine-receptor mutation appeared to have been hypersensitive to the air puffs. They also took much longer to calm down in contrast to ‘normal’ flies without the mutation.
What is astonishing about this finding is that earlier studies in both flies and vertebrates had suggested that dopamine apparently promotes activity. However, the experiments in this study seem to have uncovered a function of dopamine in the opposite direction. Since removing the receptor may cause hypersensitivity to the air puffs, these findings suggested that dopamine actively inhibits the hyperactivity response.
Evidently, this observation suggested a potential link to ADHD, a behavioral disorder characterized by impulsivity, hyperactivity, and short attention span. It was observed that humans with the disorder frequently take drugs such as Ritalin. Ritalin is known to increase levels of brain dopamine in order to decrease hyperactivity.
The ways the mutant flies respond to the air puffs could moreover suggest the way in which individuals with ADHD display hypersensitivity to environmental stimuli. Also, they appear to be more easily aroused by such influences. Significantly, ADHD was noted to have been genetically linked to abnormalities of the dopamine system in humans. This could in turn further strengthen the analogy between the mutant flies and this psychiatric disorder.
There may also be another possible link that is some individuals with ADHD display learning disabilities. Similarly, study authors from Pennsylvania State University seemed to have shown previously that flies with the same dopamine receptor mutation are unable to learn to associate a particular odor with an electric shock. More so, they may not avoid the odor when later tested; this is because flies without the mutation rapidly learn to make the association.
It is often assumed that because individuals with ADHD are hyperactive and easily distracted, they appear to have difficulty learning. However, the authors showed that hyperactivity and learning disabilities may not causally be related in flies bearing the dopamine receptor mutation. This in turn disproves the theory, at least in flies.
Anderson further said that, “We could separately ‘rescue’ the hyperactivity and learning deficits in a completely independent manner by genetically restoring the dopamine receptor to different regions of the fly’s brain.”
As a result, in dopamine-receptor-mutant flies, hyperactivity does not seem to cause learning deficits. Instead, these two ‘symptoms’ apparently reflect independent effects of the mutation that manifest themselves in distinct brain regions.
“The finding that flies exhibit emotion-like behaviors that are controlled by some of the same brain chemicals as in humans opens up the possibility of applying the powerful genetics of this ‘model organism’ to understanding how these chemicals influence behavior through their actions on specific brain circuits. While the specific details of where and how this occurs are likely to be different in flies and in humans, the basic principles are likely to be evolutionarily conserved, and may aid in our understanding of what goes wrong in disorders such as ADHD,” elucidates Anderson.
This finding in flies could increase the likelihood that hyperactivity and learning deficits also may not be causally linked in humans with ADHD. If so, it eventually may prove more effective to develop drugs to treat these two symptoms separately, instead of trying to cure them both with the broad-spectrum pharmaceuticals. Also, these existing pharmaceuticals available are known to have many undesirable side effects.
The findings of the study have been published in the journal, Neuron.