From the FMS Global and UK News Desk of Jeanne Hambleton
Contact Michael C. Purdy (firstname.lastname@example.org) 314-286-0122
Courtesy Eureka Alert and Washington University School of Medicine
St. Louis, March 30, 2009
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.
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 cannot 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 do not 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.
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 did not 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 is not also associated with cell survival.
“That is 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.
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.
Sleep: Spring cleaning for the brain?
Contact: Susan Lampert Smith (email@example.com) 608-262-7335
University of Wisconsin-Madison – Courtesy Eureka Alert
If you have ever been sleep-deprived, you know the feeling that your brain is full of wool.
Now, a study published in the April 3 edition of the journal Science has molecular and structural evidence of that woolly feeling — proteins that build up in the brains of sleep-deprived fruit flies and drop to lower levels in the brains of the well-rested. The proteins are located in the synapses, those specialized parts of neurons that allow brain cells to communicate with other neurons.
Sleep researchers at the University of Wisconsin-Madison School of Medicine and Public Health believe it is more evidence for their theory of “synaptic homeostasis.” This is the idea that synapses grow stronger when we are awake as we learn and adapt to an ever-changing the environment, that sleep refreshes the brain by bringing synapses back to a lower level of strength. This is important because larger synapses consume a lot of energy, occupy more space and require more supplies, including the proteins examined in this study.
Sleep — by allowing synaptic downscaling — saves energy, space and material, and clears away unnecessary “noise” from the previous day, the researchers believe. The fresh brain is then ready to learn again in the morning.
The researchers — Giorgio Gilestro, Giulio Tononi and Chiara Cirelli, of the Center for Sleep and Consciousness — found that levels of proteins that carry messages in the synapses (or junctions) between neurons drop by 30 to 40 percent during sleep.
In the Science paper, three-dimensional photos using confocal microscopy show the brains of sleep-deprived flies filled with a synaptic protein called Bruchpilot (BRP), a component of the machinery that allows communication among neurons. In well-rested flies, levels of BRP and four other synaptic proteins drop back to low levels, providing evidence that sleep resets the brain to allow more growth and learning the next day.
“We know that sleep is necessary for our brain to function properly, to learn new things every day, and also, in some cases, to consolidate the memory of what we learned during the day,” says Cirelli, associate professor of psychiatry.
“During sleep, we think that most, if not all, synapses are downscaled: at the end of sleep, the strongest synapses shrink, while the weakest synapses may even disappear.”
The confocal microscope views show this happening in all three major areas of the fruit-fly brain, which are known to be very plastic (involved in learning).
In a paper published last year, Tononi, Cirelli and their co-investigators found similar chemical changes in the synapses of rats’ brains. They also showed that rats’ brains have a stronger “evoked response” to electrical stimulation after being awake, and a weaker one after sleep. That finding provided more evidence, using electrophysiological rather than molecular techniques, consistent with the idea that synapses grow stronger during the day, then weaker during sleep.
Because sleep performs the same function in the brains of species as diverse as fruit flies and rats, Cirelli says it was likely conserved by evolution because it is so important to an animal’s health and survival.
The Wisconsin laboratory has pioneered ways of studying sleep in different species, including fruit flies.
To keep the flies awake, they are put into a “fly agitator” that holds 10 plates, each containing 32 drowsy flies. A robot arm shakes the plates occasionally to keep the flies from dozing.
Flies were deprived of sleep for as long as 24 hours. Researchers then dissected their brains and measured the levels of four pre-synaptic proteins and one post-synaptic protein. All levels rose progressively during periods of wakefulness and fell after sleep. Other experiments confirmed that the changes in protein levels were not caused by exposure to light and darkness or by the stimulation itself, but by sleep and waking. They also used confocal microscopy and an antibody that specifically recognizes BRP to measure the expression of this protein in many fly-brain areas.
Higher levels of these synaptic proteins during waking may be evidence of random experiences that fill the brain every day and need to be dissipated to make room for the learning and memories that are truly significant.
“Much of what we learn in a day, we do not really need to remember,” Cirelli says. “If you have used up all the space, you cannot learn more before you clean out the junk that is filling up your brain.”