Fruit Flies In Dreamland? "Dozing" Invertebrates May Stir New Sleep-Disorder Studies

The common fruit fly, Drosophila melanogaster, seems to undergo behavioral and molecular changes similar to those observed among mammals, says lead Science author Paul J. Shaw of The Neurosciences Institute in San Diego, California. Like human sleep, a fly's beauty rest can be altered by caffeine or antihistamines, for example, and sleep deprivation prompts it to overcompensate by catching a few extra winks.

Most importantly, the Science authors say, the fruit fly seems to share several molecular markers believed to modulate sleep and waking in mammals. Of particular interest was an enzyme that regulates levels of neurotransmitters called monoamines, at least in rats.

In humans, sleep may be important for breaking down and lowering brain levels of monoamines such as norepinephrine and serotonin, explains Giulio Tononi, principal investigator of the study. Understanding such functions might ultimately prove helpful to people with insomnia or late-shift workers who must forego sleep on a regular basis, Tononi says. "Is it possible that a lack of sleep can damage the system because monoaminergic release is not interrupted through sleep?" he asks. "We are still in the dark about this, but at least we now have a clue where to look."

A longtime laboratory staple, the fruit fly's genetic composition is well-understood and, therefore, could serve as "a model system for elucidating the functions of sleep" in far more complex animals, according to the Science authors, including Chiara Cirelli and Ralph J. Greenspan of The Neurosciences Institute.

Among many creatures, sleep has been characterized by behavioral markers, such as restfulness, as well as biochemical evidence, including changes in the expression of certain neural genes. Invertebrates also seem to follow circadian cycles of rest and activity. Yet, researchers have been hard-pressed to determine whether drowsy insects are, in fact, asleep.

"There is no golden standard for demonstrating when an animal is asleep, and some of the traditional criteria can be extremely difficult to assess, when applied to an insect," notes Tononi, a senior fellow at The Neurosciences Institute, a not-for-profit organization. "It is difficult to get an electroencephalogram (EEG) from a fruit fly, so you have to look at behavioral criteria, such as immobility, increased thresholds for arousal, and an increased need for sleep following deprivation. These homeostatic criteria seem to be universal in birds and mammals. We observed them in fruit flies, too."

Flies in the Science study were subjected to 12-hour light/12-hour dark cycles, which prompted more than 90 percent to rest in darkness. Researchers also studied the flies' behavioral responses to sleep deprivation, induced by a gentle tapping. Most flies recovered 50 percent of the rest they lost within 24 hours--a behavior seen in humans.

But, are inactive fruit flies really sleeping? To further test this question, the Science authors analyzed molecular markers in resting versus alert specimens. In previous studies with rodents, the research team had identified several genes whose expression changes in the brain between sleeping and waking. One such enzyme was involved in breaking down or catabolyzing monoamines in rats, Tononi points out. Similarly, fruit flies with a mutated Dat gene, which codes for the brain enzyme, arylalkylamine N-acetyltransferase, needed far more rest to bounce back from sleep deprivation. Tononi speculates that the mutants couldn't break down monoamines while alert, so they needed extra dozing time to adjust their biochemistry.

The jury's still out on whether fruit flies dream, but the Science authors provide evidence to support the notion that they do sleep. Their work also sets the stage for new sleep-disorder research. "Demonstrating sleep in the fruit fly, based on behavioral and molecular markers, opens the way for using the fly for mutagenesis and for identifying genes that influence the need for sleep," Tononi says.

The Neurosciences Institute is supported by The Neurosciences Research Foundation and receives major support for this program from Novartis. Cirelli was a Joseph Drown Foundation Fellow.