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Sleep may help clear the brain for new learning

By Michael Purdy

A new theory about sleep's benefits for the brain gets a boost from fruit flies in this week's Science. Researchers at Washington University School of Medicine in St. Louis found evidence that sleep, already recognized as a promoter of long-term memories, also helps clear room in the brain for new learning.

Washington University scientists used genetically modified fruit flies to track the creation of new brain synapses, junctures where two brain cells communicate. They found that two scenarios that give the fruit fly's brain a workout caused new synapses to arise. To their surprise, all of the new synapses originated from a group of 16 cells in the fly brain's internal timekeeping mechanism. The cells are highlighted in the encircled area above.

The critical question: How many synapses, or junctures where nerve cells communicate with each other, are modified by sleep? Neurologists believe creation of new synapses is one key way the brain encodes memories and learning, but this cannot continue unabated and may be where sleep comes in.

"There are a number of reasons why the brain can't indefinitely add synapses, including the finite spatial constraints of the skull," says senior author Paul Shaw, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "We were able to track the creation of new synapses in fruit flies during learning experiences, and to show that sleep pushed that number back down."

Scientists don't yet know how the synapses are eliminated. According to theory, only the less important connections are trimmed back, while connections encoding important memories are maintained.

Many aspects of fly sleep are similar to human sleep; for example, flies and humans deprived of sleep one day will try to make up for the loss by sleeping more the next day. Because the human brain is much more complex, Shaw uses the flies as models for answering questions about sleep and memory.

Washington University's Paul Shaw, Ph.D., and Jeff Donlea, a graduate student, used this microscope to study the brains of fruit flies. The researchers found evidence that sleep, long suspected to play a role in the establishment of long-term memories, also helps clear the way for the creation of new memories in the days to come.

Sleep is a recognized promoter of learning, but three years ago Shaw turned that association around and revealed that learning increases the need for sleep in the fruit fly. In a 2006 paper in Science, he and his colleagues found that two separate scenarios, each of which gave the fruit fly's brain a workout, increased the need for sleep.

The first scenario was inspired by human research linking an enriched environment to improved memory and other brain functions. Scientists found that flies raised in an enhanced social environment—a test tube full of other flies—slept approximately 2-3 hours longer than flies raised in isolation.

Researchers also gave male fruit flies their first exposure to female fruit flies, but with a catch—the females were either already mated or were actually male flies altered to emit female pheromones. Either fly rebuffed the test fly's attempts to mate. The test flies were then kept in isolation for two days and exposed to receptive female flies. Test flies that remembered their prior failures didn't try to mate again; they also slept more. Researchers concluded that these flies had encoded memories of their prior experience, more directly proving the connection between sleep and new memories.

Scientists repeated these tests for the new study, but this time they used flies genetically altered to make it possible to track the development of new synapses, the junctures at which brain cells communicate.

"The biggest surprise was that out of 200,000 fly brain cells, only 16 were required for the formation of new memories, " says first author Jeffrey Donlea, a graduate student. "These sixteen are lateral ventral neurons, which are part of the circadian circuitry that let the fly brain perform certain behaviors at particular times of day."

When flies slept, the number of new synapses formed during social enrichment decreased. When researchers deprived them of their sleep, the decline did not occur.

Donlea identified three genes essential to the links between learning and increased need for sleep: rutabaga, period and blistered. Flies lacking any of those genes did not have increased need for sleep after social enrichment or the mating test.

Blistered is the fruit fly equivalent to a human gene known as serum response factor (SRF). Scientists have previously linked SRF to plasticity, a term for brain change that includes both learning and memory and the general ability of the brain to rewire itself to adapt to injury or changing needs.

The new study shows that SRF could offer an important advantage for scientists hoping to study plasticity: unlike other genes connected to plasticity, it's not also associated with cell survival.

"That's going to be very helpful to our efforts to study plasticity, because it removes a large confounding factor," says co-author Naren Ramanan, Ph.D., assistant professor of neurobiology. "We can alter SRF activity and not have to worry about whether the resulting changes in brain function come from changes in plasticity or from dying cells."

Shaw plans further investigations of the connections between memory and sleep, including the question of how increased synapses induce the need for sleep.

"Right now a lot of people are worried about their jobs and the economy, and some are no doubt losing sleep over these concerns," Shaw says. "But these data suggest the best thing you can do to make sure you stay sharp and increase your chances of keeping your job is to make getting enough sleep a top priority."


Donlea JM, Ramanan N, Shaw PJ. Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science, April 3, 2009.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

MEDIA CONTACTS
Michael Purdy
Senior Medical Sciences Writer
(314) 286-0122
purdym@wustl.edu
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