Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Caltech scientists find emotion-like behaviors, regulated by dopamine, in fruit flies

27.11.2009
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.

There is also another possible link: some individuals with ADHD display learning disabilities. Similarly, researchers from Pennsylvania State University—who collaborated on the Neuron study—have shown previously that flies with the same dopamine receptor mutation are unable to learn to associate a particular odor with an electric shock, and do not avoid the odor when subsequently tested. (Flies without the mutation quickly learn to make the association.)

It is often assumed that because individuals with ADHD are hyperactive and easily distracted, they have difficulty learning. The Caltech group showed, however, that hyperactivity and learning disabilities are not causally related in flies bearing the dopamine receptor mutation, thereby disproving the theory—at least in flies.

"We could separately 'rescue' the hyperactivity and learning deficits in a completely independent manner," says Anderson, "by genetically restoring the dopamine receptor to different regions of the fly's brain."

Thus, in dopamine-receptor-mutant flies, hyperactivity does not seem to cause learning deficits. Instead, these two "symptoms" reflect independent effects of the mutation that manifest themselves in distinct brain regions. "Being able to observe and manipulate the different neural substrates for learning and arousal will hopefully give us a unique method for identifying new molecular pathways that could be investigated and validated in higher organisms," says Lebestky.

This finding in flies, notes Anderson, raises the possibility that hyperactivity and learning deficits also may not be causally linked in humans with ADHD. If so, he says, it ultimately may prove more effective to develop drugs to treat these two symptoms separately, rather than trying to cure them both with the broad-spectrum pharmaceuticals currently available, which have many undesirable side effects.

"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," says Anderson. "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."

In addition to Lebestky, Anderson, and Perona, other researchers on the Neuron paper, "Two Different Forms of Arousal in Drosophila are Oppositely Regulated by the Dopamine D1 Receptor Ortholog DopR via Distinct Neural Circuits," are Jung-Sook Chang, Heiko Dankert, and Lihi Zelnik from Caltech; Young-Cho Kim and Kyung-An Han from Pennsylvania State University; and Fred Wolf from the University of California, San Francisco. Their work was funded by grants from the National Science Foundation and the Howard Hughes Medical Institute.

Lori Oliwenstein | EurekAlert!
Further information:
http://www.caltech.edu
http://media.caltech.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>