As things stand now, there are two alternating modes of existence, sleep and wakefulness, which provide the background for every human function. Though we seem relatively flexible in our sleeping and waking behavior on a moment to moment basis, in that we can wake up and do things at almost anytime of the day or night we choose, the need to sleep actually has an awesome power over our lives. If we go without sleep or drastically reduce it, the desire or need to sleep quickly becomes more important than life itself. Sleep is so preemptive, that we cannot stay awake even to avoid death. Thus, the train crews that died in the head-on collision near Thompson Point, Pennsylvania, at 5:30 a.m. on January 14, 1988, or in Colorado at 3:00 a.m. in 1984, died because they fell asleep; at some point they must have known that falling asleep was linked with their eventual doom. Perhaps there came a moment when sleepiness severely impaired their judgment--and then it was too late. This intense sleepiness, the extreme difficulty of maintaining wakefulness for more than two or three days, the willingness to put one's life at risk . . . this compelling need to sleep is so powerful that it cannot be avoided. Thus, the willingness to put one's life at risk in order to obtain even a little sleep strongly suggests that sleep is vitally necessary for our health and survival. In addition, human beings spend an enormous amount of time sleeping. They organize their time, their recreation, their very society to meet the demands for sleep. Caves, huts, houses, hotels, and apartment buildings are all clustered together so we can be safe and secure as we pass the night in the arms of the Morpheus . There were early notions that life was carried on in the sunlight, that the reduced stimulation of darkness could not sustain wakefulness, and that supernatural beings peopled the dark. Who knows? What we do know is that life and activity are as much a part of the night as the day, and that high levels of activity and the performance of vital functions are as much a part of sleep as of wakefulness.

If some function of the brain takes place during sleep simply because it is easier to do so, could it take place in the waking brain if sleep did not exist? If not, could we then exist? At any rate, the mysteries of sleep? . . . Why we sleep? How we sleep? What we do during sleep? . . . are just as exciting as the other mysteries that surround us--the why's and how's of the cosmos and consciousness. Why curiosity alone has not impelled countless scientists to pursue these mysteries is difficult to understand. Perhaps the stereotype of sleep as a brain turned off and the difficulty of studying sleep without disturbing it might be explanations. Another is that it takes great imagination to explore where no one has gone before--to take the creative leap to appreciate the fact that the sleeping brain is a brain, equally and perhaps more active, than the waking brain.

To discuss this further, we need to ask the question, "What is Sleep?"

It must immediately be pointed out that the problem of defining sleep was greatly complicated just a couple of decades ago when it was realized that rapid eye movements (REMs) during sleep were a marker of a biological state which was so markedly different from the remainder of sleep as to require its very own name--REM sleep. REM sleep is a state during which binocularly synchronous rapid eye movements are seen, muscle atonia* occurs and the activity of the autonomic nervous system is irregular and accelerated. Measures of central nervous system activation strongly suggest that the brain reaches peak activity during REM sleep. NREM sleep, by contrast, lacks the visible motility of eye movements and twitches, has a totally different EEG* pattern, which is synchronized and slow, and appears to present more regular patterns of autonomic function. Forced to give up the notion that sleep is generally associated with lowered brain activity, theorists of the day continued, however, to attribute this property to NREM sleep.

It is difficult to understand the popular stereotype of sleep as the brain turned off, which is analogous to a car sitting in a garage with the ignition turned off and the motor silent. This point of view also underlies a metaphorical mythology that the brain must "rest." It is no more conceivable that the brain needs to rest than that the liver needs to rest.

Most definitions of sleep are stated in terms of various phenomena or internal processes that go on during sleep; for the most part, these definitions are very superficial. Thus, relative immobility is a property of sleep. On the other hand, if we are rigorous, immobility is not essential (i.e., rolling over in bed, rapid movement of our eyes). A synchronized electroencephalogram is a concomitant of NREM sleep. Early generalizations that this reflects slow, synchronized, neuronal firing patterns were commonplace. Actually, neuronal activity is extremely brisk in a number of key areas in the brain during NREM sleep. More sophisticated measures of motor activity reveal that during REM sleep there is a suppression of voluntary motor functions and depression of various somatic reflexes. On the other hand, during REM sleep the brain, in terms of several measures, is clearly more active than during wakefulness.

One of the greatest needs, in terms of clarifying the nature of sleep, is to obtain a consensus on the key processes that act differently during sleep compared with wakefulness and to understand the mechanisms that are responsible for these differences. From a purely descriptive point of view, we need to know what is going on in the brain during sleep. For example, we need to know as much as possible about unique metabolic activity during sleep, gene expression during sleep and neurosecretion during sleep.

An essential difference between normal wakefulness and normal sleep is the degree of perception. During wakefulness we perceive and are conscious of the external world. We are engaged with it and we respond to it. The function of wakefulness seems, obviously, to foster our survival, to engage the real world, to find food, to reproduce, etc.

The fundamental essence of sleep seems to be disengagement from the outer world, and to some extent an engagement with the inner world, the dream world. This disengagement from the real world is an active process in which sensory input is blocked or modified to a level that results in perceptual blindness and deafness. We know that signals are received by the retina, transmitted to the thalamus and to the visual cortex; the same is true in the auditory system. Yet, we have no idea why, in one second, we see an object in the real world, are conscious of it, perceive it, yet in the very next second, at the moment of sleep, we become subjectively blind and do not see it at all. A dramatic example is the activity of visual cortex neurons as a cat passes from wakefulness to sleep. Often, no change whatsoever can be detected, although the behavioral, perceptual change is one of the most dramatic and abrupt in all of the animal's neurobehavioral repertoire.

Given that sleep is highly active and organized, it should not be surprising that many factors can disrupt and impair its functions. When sleep researchers began to measure a variety of functions during sleep in people who complained about their sleep or about their inability to stay awake, many previously unknown sleep disorders were discovered. In addition, they often showed a very high prevalence. At the current time, sleep disorders medicine is a flourishing clinical practice in the United States. Many occupations that are associated with the loss of sleep and the development of excessive sleepiness, which in turn impair the quality of life, also impair function and create enormous hazards. Such performance failures can kill, maim or destroy property, or lead to catastrophes invoking the failure of night workers to respond in the Chernobyl disaster, the Three Mile Island disaster or when there was a sleep loss impaired decision to launch the Challenger.

This syllabus will present a host of issues. In some areas, we know almost nothing; in other areas we know a great deal. All the knowledge and the questions are exciting and challenging. When we consider the process of being either awake or asleep, we first must realize that sleep is regulated by a biological clock by a homeostatic process in which less sleep is generally followed by more sleep and more sleep is followed by less sleep. Issues of the biological clock and the timing of sleep and wakefulness will be discussed, as will the homeostatic processes of sleep loss, and what we know about the neuroanatomical and neurochemical substrates of sleep mechanisms. We will also point out the myriad changes that occur throughout all bodily systems during sleep.