Yet Another Reason to Hit that Snooze Button

Image: Courtesy of Matthew Wilson, ©2002 Cell Press NOT A CREATURE WAS STIRRING, NOT EVEN A ... RAT that sleeps while the activity of hippocampal neurons, measured before its nap when the animal ran in a maze are behind it. Red depicts maze locations where the neuron was highly active; blue indicates where the neuron was not. Most people require sleep to face tomorrow with a clear head. But clarity of mind may be just one reason why slumber is needed; a growing body of research suggests that sleep aids learning. It is a view not universally held, but supporting evidence appears to be growing. "We just don't know right now if it will turn out to be true. There is so much data coming out now," says Pierre Maquet, senior research associate, National Fund for Scientific Research, University of Liege, Belgium. "These data are coming from a wide variety of species, techniques, experimental paradigms. There is something behind it." Daniel Margoliash, professor of organismal biology and anatomy, University of Chicago, says, "A substantial percentage of the scientific population ... is still quite skeptical." Researchers have data supporting the link between sleep and memory from studies with humans, rats, and birds, in which the subjects perform numerous learning tasks.1 The studies focus on two specific parts of sleep--slow wave sleep (SWS) and rapid eye movement (REM) sleep. SWS is deep slumber marked by large-amplitude electroencephalogram (EEG) patterns. REM is characterized by high-frequency, low-amplitude EEGs and decreased muscle tone. These stages appear to have two different functions, says Robert Stickgold, assistant professor of psychiatry, Harvard Medical School. SWS strengthens memories or connections already in progress, but it does not help connect memories to one another. "I think REM sleep is going to turn out to be most relevant to ... associative and connective processes in memory," he says. A GOOD NIGHT'S LEARNING Matthew Wilson, associate professor in the Center for Learning and Memory at the Massachusetts Institute of Technology, studies the relationship between maze learning and sleep. He found that the hippocampus, a brain structure involved in spatial learning, appears to show the same activity pattern during sleep as when animals learn the maze.2 After research subjects awoke from SWS, their hippocampi retrieved recently acquired memory, Wilson says, witnessed at the level of patterns in the hippocampi's neurons. "One could describe what goes on in slow wave sleep as a replay of recent experience." Known as a sharp wave or activity spike, this hippocampal activity, which lasts about 100 milliseconds, appears to be tightly linked to cortical activity, explains psychology professor Bruce McNaughton, University of Arizona. During the slow wave phase, he says, cortical activity fluctuates between bursts of activity and so-called downtime periods of little or no activity. These fluctuations, long recognized, seem to occur almost randomly. "Recent [unpublished] evidence we have in the rat suggests that if the cortex falls silent, the very next sharp wave that comes out of the hippocampus bumps it back up into an active state, as though the sharp wave were sending a packet of information.3 The cortex goes on processing after the sharp wave," McNaughton says. He describes the hippocampus as "orchestrating" cortical activity. Describing his thinking as "pure speculation," McNaughton talks of the hippocampus sending a code that tells the cortex to activate and process a specific memory. "The hippocampus is getting these things out and stabilized in the cortex," says Stickgold. In a simple visual discrimination task, researchers asked human subjects to determine the orientation of lines on a screen. The participants' improvement was related both to the amount of early slow wave and deep sleep they received in the sleep cycle's last quarter. "Sleep within 30 hours of training is absolutely required for improved performance," Stickgold says. REM sleep, he says, is important because it plays a role in associations and context. It pulls together a collection of images and facts; just how this happens is still a mystery, says Stickgold. IS SLEEP REALLY NECESSARY? At least one research-er is interested in quiescence --a quiet, sleep-like state. McNaughton is exploring its impact on memory. Using electrodes, McNaughton and colleagues are studying the cortical patterns of monkeys. After learning a task in which the monkeys reach and then withdraw their arms, they are placed in a darkened room. While there, the animals are quiescent and pay no attention "to what's going on around [them]," says Mc-Naughton. He expects the cortical electrical patterns will be similar to those seen during periods when the monkeys are awake and engaged in the reaching task. His reasoning is based on findings in the rat brain, in which the hippocampus shows sharp waves not only during sleep, but also at other times when the animal is "not engaged in processing external input." Image: Courtesy of Jerry Siegel, ©2001 AAAS TO SLEEP, PERCHANCE TO LEARN? Don't count on it, some say: Daily REM sleep time in mammals does not positively correlate with learning ability. Pictured are REM sleep hours and total sleep across the 24-hour cycle for each animal pictured as compared to humans. (Reprinted with permission of AAAS) Understanding what might be happening during such a quiescent state is vital in understanding sleep and memory, Maquet says. "Is it really the way neurons are firing when you're asleep that make sleep fertile for memory consolidation or [can] any type of quiescence ... do it?" Furthermore, Maquet says, even if an animal is awake, certain brain neurons could be firing in a mode that resembles the ones observed during sleep, as found in a recent study in cats that found such activity in the occipital cortex.4 A full night's sleep may not be required; Stickgold and his colleagues found that a simple nap can help memory.5 COULD BIRDS HOLD THE ANSWER? Re-searchers are also studying songbirds to understand sleep and memory. Ofer Tchernichovski, associate professor of biology, City College, City University of New York, says that learning a complete song is a bird's target, and the animal focuses on doing so within a number of weeks. He found, using minute-by-minute analyses of zebra finch songs, that birds did not show that they learned their songs until they had a night's sleep.6 Because that finding was not predicted but was discovered when the results were analyzed, Tchernichovski is conducting further research comparing such variables as accuracy and pitch in the evening and morning songs. The initial finding was "surprising and compelling," says Margoliash, whose own research found that a part of the brain, the robustus archiastralis (RA), shows the same sort of activity during sleep as it does when the bird is singing,7 leading him to believe in the importance of sleep in bird-song learning. Margoliash wants to determine if inhibiting RA activity during sleep will interfere with learning--an important experiment in demonstrating a causal connection. Such an approach may avoid creating stress that would arise with sleep deprivation, confounding the results. ON THE OTHER HAND... Jerome Siegel, professor of psychiatry, University of California, Los Angeles, and chief of neurobiology research, Veteran's Affairs Medical Center, Sepulveda, Calif., argues that no evidence exists showing that sleep is needed for learning or memory consolidation. He points to numerous studies, which he claims show that individuals deprived of SWS and REM sleep still learn new tasks. "I think there's nothing there," he says. "People [who] do not have REM sleep have normal or improved memory. People with brain damage that prevents REM sleep do not appear to have [a] memory deficit."8,9 Niels Rattenborg, an assistant scientist in the Psychiatric Institute, University of Wisconsin, Madison, is studying the learning ability of migratory birds. It has long been presumed, he says, that when traveling, such birds fly at night and remain awake during the day. By manipulating light and dark, Rattenborg is inducing migratory behavior in captive birds from a migrating subspecies of white crown sparrows. He is hoping to see what these birds do at night, and he plans to test their new-task learning abilities. "This will be the first study to record their sleep behavior and electrophysiology during migration. If we confirm they aren't sleeping much, and it might be for weeks at a time, the compelling question is how are they functioning without much sleep? Are they able to learn?" Rattenborg says he believes that they can; otherwise this behavior would be selected against. "So I suspect they've found a way to suspend the need for sleep," he states. Rattenborg plans to compare these birds to a nonmigrating subspecies of the white crowned sparrow. "If we find the [migrating] birds are fully capable of learning despite not sleeping, it will challenge the theories that sleep is for learning." Harvey Black (hblack@chorus.net) is a freelance writer in Madison, Wis. References 1. P. Walker et al., "Practice with sleep makes perfect: Sleep dependent motor skill learning," Neuron, 35:1-20, July 3, 2002. 2. M.A. Wilson, B.L. McNaughton, "Reactivation of hippocampal ensemble memories during sleep," Science, 65:676-9, 1994. 3. F.P. Battaglia et al., "Widespread modulation of neocortical cell activity during hippocampal sharp wave," Society for Neuroscience Abstracts, 27:1699, 2001. 4. R. Stickgold, "Visual discrimination learning requires sleep after training," Nature Neuroscience, 3:1237-8, 2000. 5. I. N. Pigarev et al., "Evidence for asynchronous development of sleep in cortical areas," Neuroreport, 11:2557-60, 1997. 6. S.C. Mednick et al., "The restorative effect of naps on perceptual deterioration," Nature Neuroscience, 5:677-81, July 2002. 7. O. Tchernichovski et al., "Dynamics of the vocal imitation process: How a zebra finch learns its song," Science, 291:2564-9, 2001. 8. J. Siegel, "The REM sleep-memory consolidation hypothesis," Science, 294:1058-63, 2001. 9. F. Valledoriola et al., "Absence of REM sleep, altered NREM sleep and supranuclear horizontal gaze palsy caused by a lesion of the pontine tegmentum," Sleep, 16:184-8, 1993.

Yet Another Reason to Hit that Snooze Button

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Image: Courtesy of Matthew Wilson, ©2002 Cell Press
NOT A CREATURE WAS STIRRING, NOT EVEN A ... RAT that sleeps while the activity of hippocampal neurons, measured before its nap when the animal ran in a maze are behind it. Red depicts maze locations where the neuron was highly active; blue indicates where the neuron was not.