WHY WE SLEEP

The reasons that we sleep are gradually becoming less enigmatic

By Jerome M. Siegel

irds do it, bees do it,

and, in a departure from the Cole if incomplete, guideline about sleep. Despite the difficulty in
Porter song lyrics, even fruit flies appear to do it. Humans cer- strictly defining sleep, an observer can usually tell when a sub-
tainly do it. The subject is not love, but sleep. Shakespeare’s ject is sleeping: the sleeper ordinarily exhibits relative inatten-
Macbeth said it “knits up the raveled sleave of care” and was tion to the environment and is usually immobile. (Dolphins and
the “balm of hurt minds, great nature’s second course, chief other marine mammals swim while sleeping, however, and
nourisher in life’s feast.” Cervantes’s Sancho Panza sang its some birds may sleep through long migrations.)
praises as “the food that cures all hunger, the water that In 1953 sleep research pioneer Nathaniel Kleitman and his
quenches all thirst, the fire that warms the cold, the cold that student Eugene Aserinsky of the University of Chicago decisively
cools the heart ... the balancing weight that levels the shepherd overthrew the commonly held belief that sleep was simply a ces-
with the king, and the simple with the wise.” sation of most brain activity. They discovered that sleep was
The simple and the wise have long contemplated two re- marked by periods of rapid eye movement, commonly known
lated questions: What is sleep, and why do we need it? An ob- now as REM sleep. And its existence implied that something ac-
vious answer to the latter is that adequate sleep is necessary tive occurred during sleep. All terrestrial mammals that have
to stay alert and awake. That response, however, dodges the been examined exhibit REM sleep, which alternates with non-
issue and is the equivalent of saying that you eat to keep from REM sleep, also called quiet sleep, in a regular cycle.
being hungry or breathe to ward off feelings of suffocation. More recently, the field has made its greatest progress in
The real function of eating is to supply nutrients, and the func- characterizing the nature of sleep at the level of nerve cells (neu-
tion of breathing is to take in oxygen and expel carbon diox- rons) in the brain. In the past 20 years, scientists have mastered
ide. But we have no comparably straightforward explanation techniques for guiding fine microwires (only 32 microns wide,
for sleep. That said, sleep research— less than a century old as comparable to the thinnest of human hair) into various brain
a focused field of scientific inquiry— has generated enough in- regions. Such wires produce no pain once implanted and have
sights for investigators to at least make reasonable proposals been used in humans as well as in a wide range of laboratory
about the function of the somnolent state that consumes one animals while they went about their normal activities, includ-
third of our lives. ing sleep. These studies showed, as might be expected, that
most brain neurons are at or near their maximum levels of ac-
What Is Sleep? tivity while the subject is awake. But neuronal doings during
U . S . S U P R E M E C O U R T J U S T I C E Potter Stewart’s famous sleep are surprisingly variable. Despite the similar posture and
quote about obscenity— “I know it when I see it”— is a useful, inattention to the environment that a sleeper shows during both

92 SCIENTIFIC AMERICAN NOVEMBER 2003

 REM and non-REM sleep, the brain behaves completely dif- age because neurons are behaving individually. And most brain
ferently in the two states. cells in both the forebrain and brain stem regions are quite ac-
During non-REM sleep, cells in different brain regions do tive, signaling other nerve cells at rates as high as— or higher
very different things. Most neurons in the brain stem, immedi- than— rates seen in the waking state. The brain’s overall con-
ately above the spinal cord, reduce or stop firing, whereas most sumption of energy during REM sleep is also as high as while
neurons in the cerebral cortex and adjacent forebrain regions awake. The greatest neuronal activity accompanies the famil-
reduce their activity by only a small amount. What changes iar twitches and eye motion that give REM sleep its name. Spe-
most dramatically is their overall pattern of activity. During the cialized cells located in the brain stem, called REM sleep-on
awake state, a neuron more or less goes about its own individ- cells, become especially active during REM sleep and, in fact,
ual business. During non-REM sleep, in contrast, adjacent cor- appear to be responsible for generating this state.
tical neurons fire synchronously, with a relatively low frequen- Our most vivid dreams occur during REM sleep, and
cy rhythm. (Seemingly paradoxically, this synchronous elec- dreaming is accompanied by frequent activation of the brain’s
trical activity generates higher-voltage brain waves than waking motor systems, which otherwise operate only during waking
does. Yet just as in an idling automobile, less energy is con- movement. Fortunately, most movement during REM sleep
sumed when the brain “idles” in this way.) Breathing and heart is inhibited by two complementary biochemical actions in-
rate tend to be quite regular during non-REM sleep, and reports volving neurotransmitters, the chemicals that physically car-
of vivid dreams during this state are rare. ry signals from one neuron to another at the synapse (the con-
A very small group of brain cells (perhaps totaling just tact point between two neurons). The brain stops releasing
100,000 in humans) at the base of the forebrain is maximally neurotransmitters that would otherwise activate motoneurons
active only during non-REM sleep. These cells have been called (the brain cells that control muscles), and it dispatches other
sleep-on neurons and appear to be responsible for inducing neurotransmitters that actively shut down those motoneurons.
sleep. The precise signals that activate the sleep-on neurons are These mechanisms, however, do not affect the motoneurons
not yet completely understood, but increased body heat while that control the muscles that move the eyes, allowing the rapid
an individual is awake clearly activates some of these cells, eye movements that give the REM sleep stage its name.
which may explain the drowsiness that so often accompanies a REM sleep also profoundly affects brain systems that control
MINDY JONES

hot bath or a summer day at the beach. the body’s internal organs. For example, heart rate and breath-
On the other hand, brain activity during REM sleep re- ing become irregular during REM sleep, just as they are during
sembles that during waking. Brain waves remain at low volt- active waking. Also, body temperature becomes less finely reg-

www.sciam.com SCIENTIFIC AMERICAN 93

 ulated and drifts, like that of a reptile, to- In humans, a very rare degenerative larities might also be expected to have
ward the environmental temperature. In brain disease called fatal familial insom- similar sleep habits. Yet studies of labo-
addition, males often get erections and fe- nia leads to death after several months. ratory, zoo and wild animals have re-
males experience clitoral enlargement, al- Whether the sleep loss itself is fatal or vealed that sleep times are unrelated to
though most dream content is not sexual. other aspects of the brain damage are to the animals’ taxonomic classification: the
This brief description of sleep at the blame is not clear. Sleep deprivation range of sleep times of different primates
gross and neuronal levels is both accurate studies in humans have found that sleepi- extensively overlaps that of rodents,
and as unsatisfying as being awakened ness increases with even small reductions which overlaps that of carnivores, and so
before the completion of a good night’s in nightly sleep times. Being sleepy while on across many orders of mammals. If
slumber. The tantalizing question per- driving or during other activities that re- evolutionary relatedness does not deter-
sists: What is sleep for? quire continuous vigilance is as danger- mine sleep time, then what does?
ous as consuming alcohol prior to those The extraordinary answer is that size
The Function of Sleep tasks. But existing evidence indicates that is the major determinant: bigger animals
A T A R E C E N T S L E E P conference, an at- “helping” people to increase sleep time simply need less sleep. Elephants, giraffes
tendee commented that the function of with long-term use of sleeping pills pro- and large primates (such as humans) re-
sleep remains a mystery. The chair of the duces no clear-cut health benefit and may quire relatively little sleep; rats, cats,
session argued vehemently against that actually shorten life span. (About seven voles and other small animals spend most
position— she did not, however, provide reported hours of sleep a night correlates of their time sleeping. The reason is ap-
a concrete description of exactly why with longer life spans in humans.) So in- parently related to the fact that small an-
sleep’s function was no longer mysteri- exorable is the drive to sleep that achiev- imals have higher metabolic rates and

REM sleep is the proverbial riddle

wrapped in a MYSTERY inside an ENIGMA.
ous. Clearly, no general agreement yet ex- ing total sleep deprivation requires re- higher brain and body temperatures than
ists. But based on the currently available peated and intense stimulation. Re- large animals do. And metabolism is a
evidence, I can put forth what many of us searchers employing sleep deprivation to messy business that generates free radi-
feel are some reasonable hypotheses. study sleep function are therefore quick- cals— extremely reactive chemicals that
One approach to investigating the ly confronted with the difficulty of dis- damage and even kill cells. High meta-
function of sleep is to see what physio- tinguishing the effects of stress from bolic rates thus lead to increased injury
logical and behavioral changes result those of sleep loss. to cells and the nucleic acids, proteins
from a lack of it. More than a decade ago Researchers also study the natural and fats within them.
it was found that total sleep deprivation sleep habits of a variety of organisms. An Free-radical damage in many body
in rats leads to death. These animals show important clue about the function of sleep tissues can be dealt with by replacing
weight loss despite greatly increased food is the huge variation in the amount that compromised cells with new ones, pro-
consumption, suggesting excessive heat different species need. For example, the duced by cell division; however, most
loss. The animals die, for reasons yet to be opossum sleeps for 18 hours a day, where- brain regions do not produce significant
explained, within 10 to 20 days, faster as the elephant gets by with only three or numbers of new brain cells after birth.
than if they were totally deprived of food four. Closely related species that have ge- (The hippocampus, involved in learning
but slept normally. netic, physiological and behavioral simi- and memory, is an important exception.)
The lower metabolic rate and brain tem-
Overview/Uncovering Sleep perature occurring during non-REM
sleep seem to provide an opportunity to
■ Researchers are still debating the function of REM and non-REM sleep and why deal with the damage done during wak-
we need both, but new findings suggest several reasonable hypotheses. ing. For example, enzymes may more ef-
■ One is that reduced activity during non-REM sleep may give many brain cells ficiently repair cells during periods of in-
a chance to repair themselves. activity. Or old enzymes, themselves al-
■ Another is that interrupted release of neurotransmitters called monoamines tered by free radicals, may be replaced by
during REM sleep may allow the brain’s receptors for those chemicals to recover newly synthesized ones that are struc-
and regain full sensitivity, which helps with regulation of mood and learning. turally sound.
■ The intense neuronal activity of REM sleep in early life may allow the brain to Last year my group at the University
develop properly. of California at Los Angeles observed
what we believe to be the first evidence for

94 SCIENTIFIC AMERICAN NOVEMBER 2003

 Sleeping, Dreaming, Waking
REM AND NON-REM SLEEP differ in several ways, some of which are illustrated below,
along with one of the proposed functions of each type of sleep.

REM SLEEP NON-REM SLEEP AWAKE

Brain stem REM-sleep-on neurons fire Forebrain sleep-on neurons fire Sleep-on neurons are inactive

Rapid eye movement

Vivid dreams occur Absence of vivid dreams Wakeful state

Certain receptors are inactive during REM

sleep, which may be necessary for their Non-REM sleep may allow cells to repair Free radicals damage cell membranes when
proper functioning during the awake state membranes damaged by free radicals neurons are active, as when we are awake

brain cell damage, in rats, occurring as a rotransmitters ceases during REM sleep, transmitter release is vital for the proper
direct result of sleep deprivation. This thereby disabling body movement and function of these neurons and of their re-
finding supports the idea that non-REM reducing awareness of the environment. ceptors (the molecules on recipient cells
sleep wards off metabolic harm. The key neurotransmitters affected— that relay neurotransmitters’ signals into
REM sleep, however, is the prover- norepinephrine, serotonin and hista- that cell). Various studies indicate that a
bial riddle wrapped in a mystery inside mine— are termed monoamines, because constant release of monoamines can de-
an enigma. The cell-repair hypothesis they each contain a chemical entity called sensitize the neurotransmitters’ recep-
could explain non-REM sleep, but it fails an amine group. Brain cells that make tors. The interruption of monoamine re-
to account for REM sleep. After all, these monoamines are maximally and lease during REM sleep thus may allow
downtime repair cannot be taking place continuously active in waking. But Den- the receptor systems to “rest” and regain
in most brain cells during REM sleep, nis McGinty and Ronald Harper of full sensitivity. And this restored sensi-
when these cells are at least as active as U.C.L.A. discovered in 1973 that these tivity may be crucial during waking for
during waking. But a specific group of cells stop discharging completely during mood regulation, which depends on the
brain cells that goes against this trend is REM sleep. efficient collaboration of neurotransmit-
KEITH KASNOT

of special interest in the search for a pur- In 1988 Michael Rogawski of the ters and their receptors. (The familiar an-
pose of REM sleep. National Institutes of Health and I hy- tidepressants Prozac, Paxil, Zoloft and
Recall that the release of some neu- pothesized that the cessation of neuro- other so-called selective serotonin reup-

www.sciam.com SCIENTIFIC AMERICAN 95

take inhibitors—SSRIs—work by causing Counting Sleep
a net increase in the amount of serotonin
BODY SIZE appears to be a major determinant in the amount of sleep that a species
available to recipient cells.)
needs. In general, the larger the animal, the less sleep it requires. Data suggest
The monoamines also play a role in that one of the functions of sleep is to repair damage to brain cells. The higher
rewiring the brain in response to new ex- metabolic rates of small animals lead to increased cellular
periences. Turning them off during REM injury and may, consequently, require more time for repair.
sleep then may be a way to prevent
changes in brain connections that might
otherwise be inadvertently created as a
result of other brain cells’ intense activi-
ty during REM.
24 Hours
Interestingly, in 2000 Paul J. Shaw
and his colleagues at the Neurosciences
Institute in La Jolla, Calif., noted a con-
nection in fruit flies between monoamine
levels and sleeplike periods, during which
the insects are relatively inactive. They
found that disrupting the flies’ downtime
led to increased levels of monoamines, as 18 14.4 12.5 10.1 8
is the case in humans. This discovery sug-
Opossum Ferret Cat Dog Human
gests that restoration of neurotransmit-
ter function, eventually to become an at- during REM sleep than during non-REM alleviate clinical depression. The mecha-
tribute of what we now know as sleep, periods supports this idea. nism for this phenomenon is unclear, but
came into being well before mammals Sleep deprivation studies indicate, one suggestion is that the deprivation
even evolved on the earth. however, that REM sleep must do more mimics the effects of SSRI antidepressants:
than prime the brain for waking experi- because the normal decrease in mono-
Other Possibilities ence. These studies show that animals amines during REM does not occur, the
WHAT ELSE MIGHT REM sleep do? made to go without REM sleep will un- synaptic concentration of neurotrans-
Researchers such as Frederick Snyder dergo more than the usual amount when mitters that are depleted in depressed in-
and Thomas Wehr of the National Insti- they are finally given the opportunity. dividuals increases.
tutes of Health and Robert Vertes of They apparently seek to make up the Some researchers are pursuing the

NINA FINKEL (chart); W. PERRY CONWAY Corbis (opossum); RENEE LYNN Photo Researchers, Inc. (elephant)
Florida Atlantic University have pro- “debt”— yet another clue that REM sleep idea that REM sleep might have a role in
posed that the elevated activity during is important. Of course, if brain arousal memory consolidation, but as I examined
REM sleep of brain cells that are not in- were the only function of REM sleep, be- in detail in a 2001 article in Science [see
volved in monoamine production en- ing awake should also pay back the debt, “More to Explore” on opposite page], the
ables mammals to be more prepared than because the waking brain is also warm evidence for that function is weak and
reptiles to cope with dangerous sur- and active. But wakefulness clearly does contradictory. The findings that argue
roundings. When waking in a cold envi- not accomplish this task. Perhaps REM against memory consolidation include the
ronment, reptiles are sluggish and require sleep debt results from the need to rest demonstration that people who have
an external heat source to become active monoamine systems or other systems that brain damage that prevents REM sleep,
and responsive. But even though mam- are “off” in REM sleep. or who have a drug-induced blockade of
mals do not thermoregulate during REM Old ideas that REM sleep deprivation REM sleep, have normal— or even im-
sleep, the intense neuronal activity dur- led to insanity have been convincingly proved— memory. And although sleep
ing this phase can raise brain metabolic disproved (although studies show that deprivation before a task disturbs con-
rate, helping mammals to monitor and depriving someone of sleep, for example centration and performance— sleepy stu-
react more quickly to a given situation on by prodding him or her awake repeated- dents do not learn or think well— REM
waking. The observation that humans ly, can definitely cause irritability). In deprivation after a period of alert learn-
are much more alert when awakened fact, REM sleep deprivation can actually ing does not appear to interfere with re-
taining the new information. In addition,
THE AUTHOR

JEROME M. SIEGEL, professor of psychiatry and a member of the Brain Research Institute dolphins experience little or no REM
at the University of California at Los Angeles Medical Center, is chief of neurobiology re- sleep yet exhibit impressive reasoning
search at Sepulveda Veterans Affairs Medical Center. Siegel is a former president of the and learning ability.
Sleep Research Society and chair of the Associated Professional Sleep Societies. In fact, learning ability across species
His recent nightly sleep time has been limited to about six hours so that he can take does not appear to be related to total
his daughter to a 7 A.M. class. REM sleep duration. Humans do not

96 SCIENTIFIC AMERICAN NOVEMBER 2003

 development, REM sleep may act as a
substitute for the external stimulation
that prompts neuronal development in
creatures that are mature at birth. Work
by Howard Roffwarg, director of the
Sleep Disorders Center at the University
of Mississippi Medical Center, and his col-
leagues support this idea. Roffwarg found
that preventing REM sleep in cats during
this early period can lead to abnormalities
in the development of the visual system.
Animals that engage in a lot of REM
sleep shortly after birth continue to expe-
rience relatively large amounts when ma-
ture. What is it about immaturity at birth
that causes REM sleep duration to be high
later in life? In simple evolutionary terms,
animals that have low REM time should
3 need less fuel and leave more descendants
than animals that experience long periods
Elephant
of high energy consumption. From that
have particularly long REM sleep times— after birth. At the other extreme, the new- perspective, it is most likely that animals
90 to 120 minutes each night—compared born dolphin can and must thermoregu- that still have high REM times must have
with other mammals. (And humans with late, swim, follow its mother and avoid evolved a use for REM sleep that is not
higher IQs or school performance do not predators. And adult dolphins, as previ- found in precocial animals. But that func-
have more, or less, REM sleep than those ously noted, do almost no REM sleeping. tion remains to be identified. Sleep re-

Time spent in REM sleep is highest early

in LIFE and falls GRADUALLY.
with lower IQs.) The amount of time Michel Jouvet, the pioneering sleep searchers are confident that progress in
spent in REM does change over an indi- researcher who discovered four decades identifying the brain regions that control
vidual’s life, however. In all animals stud- ago that the brain stem generates REM REM and non-REM sleep will soon lead
ied, the portion of each day devoted to sleep, has a provocative suggestion for to a more comprehensive and satisfying
REM sleep is highest early in the subject’s the large amounts of REM in immature understanding of sleep and its functions.
life and falls gradually to a steady, lower animals. REM sleep’s intense neuronal As we further study the mechanisms and
level in adulthood. An additional, fasci- activity and energy expenditure, Jouvet evolution of sleep, we will probably gain
nating fact emerges from comparing nu- believes, have a role early in life in estab- insights into exactly what is repaired and
merous species: the best predictor of the lishing the genetically programmed neu- rested, why these processes are best done
amount of REM sleep time for an adult ronal connections that make so-called in- in sleep, and why knitting up Shake-
in a given species is how immature the stinctive behavior possible. Before birth, speare’s raveled sleave of care ultimately
offspring of that species are at birth. or in animals that have delayed sensory helps us to stay awake.
In 1999 Jack Pettigrew and Paul
Manger of the University of Queensland MORE TO E XPLORE
in Australia and I were able to study an Encyclopedia of Sleep and Dreaming. Edited by Mary A. Carskadon. Macmillan, 1993.
unusual research subject, the platypus. Narcolepsy. Jerome M. Siegel in Scientific American, Vol. 282, No. 1, pages 76–81; January 2000.
This evolutionarily earliest of extant Principles and Practice of Sleep Medicine. Edited by Meir H. Kryger, Thomas Roth
mammals surprised us by revealing itself and William C. Dement. W. B. Saunders, 2000.
to be the champion REM sleeper: about Sleep and Dreaming. Allan Rechtschaffen and Jerome M. Siegel in Principles of Neural Science.
Fourth edition. Edited by Eric R. Kandel, James H. Schwartz and Thomas M. Jessell.
eight hours a day. The platypus is born McGraw-Hill/ Appleton & Lange, 2000.
completely defenseless and blind, cannot The REM Sleep-Memory Consolidation Hypothesis. Jerome M. Siegel in Science, Vol. 294,
thermoregulate or find food on its own, pages 1058–1063; November 2, 2001.
and stays attached to its mother for weeks Center for Sleep Research at U.C.L.A.: www.npi.ucla.edu/sleepresearch

www.sciam.com SCIENTIFIC AMERICAN 97