Brain tweak lets sleep-deprived flies stay sharp

Staying awake slows down our brains, scientists have long recognized. Mental performance is at its peak after sleep but inevitably trends downward through the day, and sleep deprivation only worsens these effects.

For the first time, School of Medicine researchers have found a way to stop this downward slide. When scientists genetically tweaked a part of the brain involved in learning and memory in fruit flies, the flies were unimpaired even after being deprived of sleep.


“The ultimate goal is to find new ways to help people like the armed forces and first responders stay alert when they have to be awake for extended periods of time,” said senior author Paul Shaw, Ph.D., assistant professor of neurobiology. “We have drugs that can keep people awake, but they’re addictive and lose their effectiveness with repeated use. This research should help us find methods for maintaining mental acuity that have more specific effects, are less addictive and retain their potency.”

The results appeared in Current Biology Aug. 5.

Shaw’s lab was the first to show that fruit flies enter a state of inactivity comparable to sleep and that the flies have periods of inactivity where greater stimulation is required to rouse them. These periods begin at night; like human sleep, they are cyclic over the course of the night, with sleep cycles lasting 20-25 minutes. Also like humans, flies deprived of sleep one day will try to make up for the lost time by sleeping more the next day.

For the new study, first author Laurent Seugnet, Ph.D., a former postdoctoral fellow, revealed that sleep deprivation impairs learning in flies. Seugnet put them through multiple runs of a maze with two options: one lighted vial with bitter-tasting quinine in it and one darkened, quinine-free vial. Flies are instinctively drawn to light but want to avoid the taste of quinine.

“This tests the flies’ mental capacity in two ways,” Seugnet said. “First, they’ve got to remember that the lighted vial is the one that has quinine in it, and then they’ve got to suppress their natural instinct to fly toward the light.”

Flies allowed normal sleep learned to avoid the lighted vial, but sleep-deprived flies did not.

A brain messenger known as dopamine is linked to some of the mental capabilities harmed by sleep loss. To see if dopamine could be used to block learning impairment in sleep-deprived flies, Seugnet genetically altered a line of flies so they made more copies of a dopamine receptor in brain regions known as the mushroom bodies. These areas are roughly equivalent to the human hippocampus involved in learning and memory.

Sleep-deprived flies with extra dopamine receptors could still learn as if they had a full night’s sleep, Seugnet found.

“Using this gene and other related genes, we may be able to find better ways to boost performance for someone like a relief worker who’s had to stay awake for six straight days trying to save people trapped by an earthquake,” Shaw said. “This type of treatment would just be for people who absolutely have to stay awake. It’s not about trying to cram too many hours in your day.”