Sleep may clear the decks for next day’s learning

Fruit fly studies find that snoozing prunes connections between brain cells

You snooze, you lose connections between brain cells, two new studies suggest.

SOCIALIZING IS TIRING SMALL PARTY. Fruit flies need more sleep after socializing, researchers at Washington University in St. Louis have discovered. They traced this increased need to 16 neurons that build connections as the flies socialize. Sleep weakens or severs some of the connections. IMAGE CREDIT: Washington University School of Medicine
MAKING CONNECTIONS Pictured are neurons, labled with green fluorescent protein, that drive fruit flies to sleep more after social interactions. Washington University School of Medicine
THIS IS A FRUIT FLY’S BRAIN ON SLEEP The longer fruit flies stay awake, the more proteins active at synapses build up (right). Sleep lowers levels of these proteins (left), indicating that one of sleep’s functions may be to reduce or eliminate synapses to make room for learning the next day. courtesy of Chiara Cirelli

People have known for some time that getting enough sleep is crucial for proper brain function. “If you don’t get enough sleep your ability to acquire, process and recall information is going to be impaired,” says Paul Shaw, a neuroscientist at Washington University in St. Louis and coauthor of one of the new studies.

But scientists debate exactly how sleep helps the brain learn and remember. Two studies appearing in the April 3 Science suggest that sleep weakens or severs connections between brain cells to make way for new information.

A study by Giorgio Gilestro, Giulio Tononi and Chiara Cirelli of the University of Wisconsin–Madison shows that proteins found in the connections between neurons, called synapses, build up in fruit fly brains while the flies are awake. Depriving flies of sleep leads to ever-greater levels of synaptic proteins, the researchers show. Levels of the proteins decrease as the flies sleep.

Scientists usually determine synapse strength by measuring electrical activity of neurons, but fruit fly brains are far too small for electrical measurements, Cirelli says. The proteins, she says, are markers of synaptic strength.

If true, the new finding would offer support for the theory of synaptic homeostasis, advanced by Tononi and Cirelli. The theory holds that sleep scales back the strength of connections between neurons, weakening the strongest connections and completely eliminating the weakest synapses. The cutbacks help save resources, the researchers say, and boost the signal of important memories over the noise of unneeded connections (SN: 12/20/08, p. 9). 

“We assume that if this is happening, it is a major function, if not the most important function, of sleep,” Cirelli says.

Other researchers have gathered conflicting data, though, suggesting that sleep aids in strengthening synapses, not weakening them.

Cirelli and Tononi’s new study is the first demonstration that sleep “does something” to synaptic connections, says Marcos Frank, a sleep researcher at the University of Pennsylvania in Philadelphia. But the technique is an indirect measure of the strength of synapses and doesn’t conclusively prove weakening of the connections. Some of his data indicate that sleep strengthens certain connections in kittens’ brains.

Cirelli says her group’s study addresses the function of sleep only in adult brains and it is too early to say whether sleep does different things to brains in young animals and people. She adds that even if isolated synapses gain strength during sleep, overall the brain loses connections during a snooze.

Frank isn’t the only skeptic of the synaptic homeostasis theory. Shaw has been studying how sleep affects learning and memory and set up his experiment, in part, to prove the idea wrong, he says. “I wasn’t buying it at the time, but the data are telling me I ought to.”

Work in Shaw’s lab previously showed that fruit flies need extra sleep after social interactions. In the new study, the researchers tracked the increased sleep drive to 16 neurons known as large lateral ventral neurons. These neurons are part of the circuitry that forms the circadian clock in the fruit fly brain. The team genetically engineered the flies to produce green fluorescent protein in neurons, making counting synapses easier. The study showed that the number of new synapses formed during social interactions decreased after flies slept. In contrast, sleep-deprived flies did not prune synapses, the researchers found. The data seems to support the theory since only sleeping flies lose synapses.

At first glance, losing synapses doesn’t seem like a good way to learn, Shaw admits. He speculates that sleep’s downsizing of the number of synapses keeps the flies’ brain circuits from getting overwhelmed by excitement and sensory input in social situations.

The new study also links learning and the need to snooze to three genes — rutabaga, period and blistered. Period was previously identified as a key gear in the fruit fly circadian clock. Blistered is the fruit fly–equivalent of human serum response factor, a gene involved in learning, memory and general brain rewiring.

Shaw says he’s not a complete convert to the synaptic homeostasis theory, though. He thinks sleep may weaken synapses in some circuits while it strengthens connections in other circuits.

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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