Dopamine could help the sleep-deprived still learn

Study is the first to reveal molecular processes that connect learning and sleep

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Dumb flies (and perhaps people) may need a little more shuteye, or a shot of dopamine, to boost their brain power.

Fruit flies need sleep in order to learn, a study in the August 5 Current Biology shows. Keeping Drosophila up for hours after their normal bedtime impaired the flies’ ability to learn a complex task.

But activating a particular receptor for the neurotransmitter dopamine in a brain structure called the mushroom bodies erased the learning deficits, researchers from WashingtonUniversity in St. Louis found.

The new study raises the possibility that learning is impaired not because sleep sneaks up on us when we’re supposed to be paying attention, but because staying awake too long erodes some biological process in the brain critical for learning and forming memories, says David Dinges, an experimental psychologist at the University of Pennsylvania School of Medicine in Philadelphia.

Such hard evidence for a direct link between sleep and learning has eluded researchers who study sleep in people and other animals, says Marcos Frank, a sleep researcher at the University of Pennsylvania School of Medicine.

That’s not for lack of trying. Scientists have amassed reams of data demonstrating behavioral evidence for the connection, but humans and other mammals are complex, making molecular studies difficult.

The research is the first to show that specific molecular changes in the brain can influence a function of sleep, Frank says.

If the same process is at work in humans, the discovery points to the possibility that drugs could one day substitute for sleep. Researchers don’t envision long-term use of such drugs, but say medications could keep soldiers alert during extended military operations and help emergency workers stay sharp after natural disasters and other crises.

The new study by Paul Shaw and colleagues takes advantage of the fruit fly’s simple brain to dissect, “in exquisite detail,” the precise role of sleep in learning, Frank says.

Shaw and his colleagues deprived fruit flies of sleep by handling them gently or by forcing the flies to walk on a fruit fly treadmill. After the fruit flies were kept up for six to 12 hours past their usual bedtimes, the researchers tested the flies’ ability to learn not to go into the light. Fruit flies are normally attracted to light, but the researchers wanted to see if the insects could learn to resist the draw. The scientists placed filter paper soaked in quinine — a substance that fruit flies don’t like — in the lighted arm of a T-shape maze. The dark arm had no quinine and lower humidity, making it the wiser choice.

Flies that got normal amounts of sleep learned to stay away from the lighted arm and wander down the dark alley instead, but sleep-deprived flies had difficulty learning to suppress their natural instinct to head for the light.

Sleepy people experience similar control problems, Shaw says. Toddlers who miss their naps can’t seem to behave and groggy adults may have trouble controlling their tempers.

“When you’re sleepy, you might snap at your coworker,” even though the person is being no more annoying than usual, Shaw says. “Sleep deprivation has a really profound effect on behavior inhibition.”

The researchers further showed that the flies’ learning problems weren’t merely due to sleepiness or to lack of motivation, two problems that confound studies in humans looking at the link between learning and sleep deprivation.

The learning deficit depended on the length of time flies were awake, with the impairment getting worse the longer the flies were kept awake.

Although the study convincingly shows that sleep deprivation disrupts learning in fruit flies, even Shaw’s “thorough” and “clever” experiments can’t determine exactly what is happening in the fruit flies’ brains, say other sleep researchers. Thus, the possibility remains that sleep may intrude during times when the flies are trying to learn, or that the flies may just not be paying attention as well when sleep deprived, these same researchers say.

“Their arguments are strong, but not watertight,” says Robert McCarley, a sleep researcher at HarvardUniversity and the Veterans Affairs Boston Healthcare System in Brockton, Mass.

Brain scans indicate that some parts of the human brain are more vulnerable to effects of sleep deprivation than others. In the fruit flies’ brains, Shaw and his colleagues traced the learning problem associated with sleep deprivation to the mushroom bodies, important structures that are involved in learning and forming memories and have other functions as well. Furthermore, the group showed that a receptor for the neurotransmitter dopamine in the mushroom bodies was important for helping fruit flies learn to avoid light.

Fruit flies, rodents, humans and other animals have multiple types of receptors for dopamine. Using drugs that block specific types of dopamine receptors, the researchers determined that the dopamine D1-like receptor (dDA1) is the critical link in the learning chain that is disrupted by sleep deprivation. Activating the dDA1 receptor only in mushroom bodies erased the learning problems in sleep-deprived fruit flies.

It’s unlikely that the fruit fly findings will translate directly into advances in human sleep research. Already scientists know that many more brain chemicals are involved in human learning and sleep and that sleep involves many parts of the brain. But the new study does suggest that dopamine may play a more important role in sleep and learning than previously suspected, says Ritchie Brown of HarvardUniversity and the Veterans Affairs Boston Healthcare System in Brockton.

Students famously use drugs, such as amphetamines and caffeine, to stay awake while studying for exams. Amphetamines increase the effective concentration of dopamine in the brain. Caffeine may indirectly affect dopamine levels.

“Up until now we’ve said that’s not a good idea because you’re losing sleep,” Brown says, but drugs that affect only a subset of dopamine receptors might well override some of the effects of sleep loss, the new study suggests. “If it holds up for rodents and humans it could certainly be very important.”

But drugs that alleviate the memory and learning deficits associated with sleep deprivation might do nothing to curb other negative effects on health, says Robert Greene, a neuroscientist at the University of Texas Southwestern Medical Center at Dallas. “There might be a piper to pay eventually,” he says.

That’s certainly true for amphetamines and caffeine, UPenn’s Dinges says. While the drugs increase alertness for a short time, eventually people crash again, and such stimulants have other side effects, such as harming heart health. “You can’t really cheat the system,” Dinges says. “It’s still true that there’s no chemical substitute for sleep.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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