Researchers identify sleep gene 27/4/05. By the University of Wisconsin Medical School Zeroing in on the core cellular mechanisms of sleep, researchers have identified a single gene mutation that has a powerful effect on the amount of time fruit flies sleep.

Most people sleep seven to eight hours a night, and if they are deprived of sleep, their cognitive performance suffers greatly. However, a few people do well with just three or four hours of sleep - a trait that seems to run in families.

"We wanted to determine which genes underlie this phenomenon in order to shed light on the mechanisms and functions of sleep," said Giulio Tononi, UW Medical School professor of psychiatry.

The researchers screened 9000 mutated fruit flies and found one line of them that slept one-third the amount of normal flies. Put through a series of tests, the short-sleeping flies, named minisleep (mns), were found to perform normally and did not appear to be impaired by sleep deprivation. The mns flies, however, did have shorter life spans.

Following the testing, the researchers noticed shaking in the flies' legs as the insects recovered from anesthesia. The observation led the team to focus on the Shaker gene, which produces this effect.

In its normal state, the Shaker gene produces an ion channel that controls the flow of potassium into cells, a process that critically affects, among other things, electrical activity in neurons. A handful of recent studies suggest that potassium channels are also involved in the generation of sleep in humans.

Genetic analysis of the mns flies revealed that their Shaker genes contained a single amino-acid mutation. Because of the mutation, a functional ion channel could not be formed on the cell membrane and potassium therefore could not flow through it.

Sleeping flies

In earlier studies, Tononi's team discovered that fruit flies do, in fact, sleep. Like humans, fruit flies generally are quiet and immobile for between six and 12 hours each night and lose most of their ability to respond to stimuli. When deprived of sleep, humans and their winged counterparts rebound on the following night by sleeping longer and more deeply. Flies also sleep more in their youth than later in life, when their sleep is fragmented, as with humans.

In other studies, the scientists also observed that caffeine has the same stimulating effects on human and fly sleep, and that similar genes are expressed in both species when they are awake and asleep. Tononi's team also conducted EEGs on the flies and found evidence of the same electrophysiological changes occurring during sleep and wakefulness as in humans.

"The electrical changes in humans look different that they do in flies because our brains are organised differently," said Chiara Cirelli, assistant professor of psychiatry at UW Medical School. "But the EEGs showed electrophysiological changes signifying that the flies were asleep and awake."

In mammals the changes produce hallmark waves, or oscillations of groups of neurons, easily detected by EEG. The waves are slower during deep sleep and faster during waking times. One way of getting from the faster to the slower state is by opening ion channels, allowing potassium to flow through them.

"Our hypothesis is that if you don't have potassium channels, you won't get slow waves," Cirelli says. "The cell membrane will remain activated, preventing long periods of deep, non-REM sleep."

The researchers say that the fly research translates to humans even more than they thought it would. "Humans have the same kind of genes and potassium channels. And we know that slow waves must be generated by changes in the excitability of neuron cell membranes," Cirelli says.

"This research offers the possibility of developing a new class of compounds that could affect potassium channels in the brain rather than other brain chemical systems targeted currently," says Chiara Cirelli, assistant professor of psychiatry at UW Medical School.

Adapted from a news release by the University of Wisconsin-Madison .

Links

Dr Giulio Tononi research page

Dr Chiara Cirelli research page

Cirelli C, et al. Reduced sleep in Drosophila Shaker mutants. Nature 2005 434: 1087-92. Abstract