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Strangest Mammal Offers Insight Into Sleep

A University of California neurobiologist has discovered some intriguing clues about the nature of sleep by studying one of nature's oddest creatures.

By Richard Karel

One of nature's great oddities may help scientists better understand one of mankind's enduring mysteries-the evolution and function of sleep.

Neurobiologist Jerome M. Siegel, Ph.D., a professor of psychiatry at the University of California at Los Angeles, and colleagues at the University of Brisbane in Queensland, Australia, have found that the duck-billed platypus, perhaps the strangest of mammals, experiences REM sleep.

The platypus is a primitive, aquatic mammal, something of a cross between a duck, a snake, and a beaver. Warm-blooded, it has the bill of a duck and lays eggs, yet suckles its young like other mammals. It has venomous spurs in its rear feet, not unlike the fangs in the mouths of poisonous snakes, and a flat, beaverlike tail. It is one of only three surviving members of the mammalian order monotreme, which includes two kinds of echidnas, or spiny anteaters, and the platypus. Until Siegel's research, monotremes were thought to lack the capacity for REM sleep.

REM, which stands for "rapid eye movement," has long been considered a hallmark of dreaming in man and, by inference, in other mammals. But the REM sleep of the platypus, unlike that of adult humans and other mammals, involves no activation of the brain's cortex. What is interesting, however, is that human neonates, like the platypus, experience REM sleep without cortical involvement. Hence, the platypus provides an evolutionary link-at least conceptually-tying together primitive and more advanced versions of REM.

Why study a mammal that looks in part like a duck but suckles like a pig? "The whole motive behind studying sleep in strange animals is to get a clue as to how sleep evolved," replied Siegel. "If you know how sleep evolved-which components came first and whether they changed in a quantitative or a qualitative way from one group of animals to another-then you can begin to see which are the central aspects, [and] which are the relatively recent aspects."

Sleep Linked to Psychiatric Disorders

Sleep researcher Eric Allen Nofzinger, M.D., is an assistant professor of psychiatry at the University of Pittsburgh's Western Psychiatric Institute and Clinic. From his perspective as a psychiatrist, said Nofzinger, it is clear that sleep is "a very important period, regardless of what it's doing because of some very important things that are going on in the brain during sleep, and because of some very characteristic alterations in sleep that occur in patients who have psychiatric disorders."

For example, depressed patients deprived of sleep for a night show significant, albeit short-lived, improvements in mood, he noted.

In addition to the link between sleep and depression, there is evidence that abnormalities in sleep cycle correlate with other psychiatric disorders, he said.

"The general sense at this point" is that non-REM sleep is more closely related to the "restorative or homeostatic" functions of sleep than is REM sleep, said Nofzinger. REM sleep is clearly different and "appears to be linked to circadian rhythms," he added.

In humans, the areas most active during REM sleep are the limbic and paralimbic structures, said Nofzinger. These are evolutionarily known to be very primitive structures of the brain, he added. They may represent "extensions of some of the brain-stem structures Dr. Siegel has found to be responsible for REM sleep in the platypus."

Both psychiatric disorders and sleep abnormalities may be linked to "basic drive states and basic brain stem functioning," he said.

PET Scans and Dreams

What does all this mean to a clinician confronted with a patient's dreams?

"I think that the emotional dream reports that people have that seem highly relevant to their own personal lives are consistent with recent research from PET imaging showing that these more primitive limbic and paralimbic structures are being activated during REM sleep," said Nofzinger. "These are the centers of the emotional regulatory structures in the brain."

Does the platypus dream? "It's hard to know what's happening" in the brain of the sleeping platypus, said Nofzinger. But since there is no cortical activation, which is understood to be necessary for visual imagery, "we would assume they don't have the imagery associated with human REM sleep," he ventured.

Although sleep abnormalities may be linked to psychiatric disorders, there is no solid evidence that depriving otherwise healthy human subjects of REM sleep creates waking pathology, according to Siegel.

The idea that REM-sleep deprivation creates pathology is "the best known nonfact in sleep research," said Siegel. "In the same way, the consolidation of learning theory [of dreams] is very attractive, but the evidence is not very impressive. It may well be that for psychiatric health in humans, REM sleep is a significant thing." It is, however, "inconceivable that the basic function of REM [sleep] is cognitive in nature."

Siegel leans toward a hypothesis that, in part, runs counter to Nofzinger's speculation that the non-REM stages of sleep are more closely involved with sleep's homeostatic and restorative functions than is REM sleep.

Is REM Restorative?

It may be that REM sleep provides a respite for the aminergic neurons regulating the release and uptake of serotonin and norepinephrine. "Clearly, one of the main neuronal events in REM sleep is the cessation of discharge of aminergic systems. This is true, at least in terms of laboratory proof, in cats and rats" and is "probably true in humans," he said.

"If you are an aminergic neuron, the biggest change in your activity" occurs not when someone is depressed or happy, but rather when he or she sleeps, said Siegel.

That is "the only time [these neurotransmitter systems] have a chance to rest." Functionally, REM sleep is the phase in which these cells are inactive while other brain cells are very active, said Siegel. But "why you need this combination of phenomena is the essence of the mystery."

Psychiatrists know that "changes in the activity of these systems and the receptor sensitivity of these systems has enormous effects on mental health." said Siegel. Sleep, in turn, has a greater impact on the activity of these systems than any other behavior, he explained.

Dreaming, concluded Siegel, "has been grafted on to a more essential primitive function, analogous to the way talking has been grafted on to breathing. The brain stem generates REM, and "the forebrain is along for the ride," he explained. "There is no question that this is true at a mechanistic level." It is clear that the limbic and paralimbic systems, "the so-called emotional regions of the brain, are very active in REM sleep," Siegel added.

Freudian and other ideas about sleep need to be reexamined, according to Siegel. "I guess I am skeptical about the idea that memories are replayed and laid down in REM sleep," said Siegel. "But it may be true that some further consolidation is going on."

What About Freud?

J. Christian Gillin, M.D., is a professor of psychiatry at the University of California San Diego and a staff psychiatrist at the Veterans Affairs San Diego Health Care System. His research involves sleep disorders in patients with depression, alcoholism, and other psychiatric problems.

"Psychiatrists have been fascinated by dreams ever since the time of Freud," said Gillin. "And we've always wondered, if, as Freud said, dreams were 'the royal road to the unconscious.' In other words, what can dreaming tell us about the human psyche and the way the brain works? Up until this research of Dr. Siegel's, it was thought these monotremes did not have REM sleep, which suggested that REM sleep might have evolved relatively late in evolutionary history."

Earlier theories suggested that REM sleep evolved in concert with and supported higher intellectual cognitive abilities, but Siegel's observations undermine this concept, Gillin remarked.

Evolutionary biologists can only infer how earlier creatures slept, since sleep "leaves no fossil record," Gillin noted. All told, humans spend a third of their lives in sleep, which makes it that much more remarkable how little scientists know about this universal human state, he observed.

"The real question for psychiatrists in particular is, What is the function of sleep? If we think of average 2-year-old humans, they spend over half their time asleep, and a very high proportion of that sleep time is REM sleep," he noted. This leads to the conclusion that "it is extremely important from an evolutionary and developmental perspective, or this wouldn't be occurring. On the other hand, there is evidence that adult humans can live without REM [sleep]."

Patients treated with MAO inhibitors, for example, completely lose the capacity for REM sleep and apparently suffer no adverse effects, said Gillin. Further evidence comes from observations of head-trauma patients, such as the Israeli soldier who lost the capacity for REM sleep subsequent to a head wound yet continued to function well.

Siegel's speculation that "sleep, particularly REM, may be changing receptor sensitivity or replenishing specific aminergic systems is intriguing but needs to be tested in some way," said Gillin.

After 30 years of studying sleep, said Gillin, he still finds it "one of the great mysteries."