Chapter 8: Sleep and Biological Rhythms
1. Describe the course of a nightís sleep: its stages and their characteristics.
2. Review the hypothesis that sleep is an adaptive response.
3. Review the hypothesis that sleep serves as a period of restoration by discussing the effects of sleep deprivation, exercise, and mental activity.
4. Discuss the functions of REM sleep.
5. Evaluate evidence that the onset and amount of sleep is chemically controlled, and describe the neural control of arousal.
6. Discuss the neural control of slow-wave and REM sleep.
7. Discuss insomnia, sleeping medications, and sleep apnea.
8. Discuss problems associated with REM and slow-wave sleep.
A PHYSIOLOGICAL AND BEHAVIORAL DESCRIPTION
Why Do We Sleep?
Sleep as an Adaptive Response
Sleep as a Restorative Process
Effects of Sleep Deprivation
Effects of Exercise on Sleep
Effects of Mental Activity on Sleep
The Functions of REM Sleep
PHYSIOLOGICAL MECHANISMS OF SLEEP AND WAKING
Chemical Control of Sleep
As we have seen, sleep is regulated; that is, if an organism is deprived of slow-wave sleep or REM sleep, the organism will make up at least part of the missed sleep when permitted to do so. In addition, the amount of slow-wave sleep that a person obtains during a day time nap is deducted from the amount of slow-wave sleep he or she obtains the next night. These facts suggest that some physiological mechanism monitors the amount of sleep that an organism receives. What might this mechanism be? Perhaps prolonged wakefulness produces a sleep-promoting substance or sleep produces a wakefullness-promoting substance.
The cerebral hemispheres of the bottlenose dolphins sleep at different times. If sleep were controlled by blood-borne chemicals, the hemispheres should sleep at the same time.
An important category of drugs, the benzodiazepines, promotes sleep. These drugs act on the benzodiazepine binding site located at the GABA receptor. The existence of a special receptor suggests the existence of at least one endogenous ligand for this receptor, and this ligand could be involved in the control of sleep. However, no one has yet discovered a benzodiazepinelike substance whose concentration in the brain varies as a function of sleepiness.
A secondary catalog of drugs affects both sleep and body temperature. For example, anti-inflammatory drugs such as aspirin and ibuprofen reduce body temperature and interfere with sleep, and a class of chemicals known as cytokines increases body temperature and produces drowsiness. Sleep and thermoregulation are closely related functions. It is possible that the anti-inflammatory drugs and the cykotines affect sleep indirectly, through their effects on body temperature.
Evidence seems to support the hypothesis that slow-wave sleep serves as a period of rest and recuperation for the brain. Presumably, increased mental activity makes the brain become "tired", and the brain displays more delta activity the following night. The primary nutrient of the brain is glucose, carried to it by the blood. The blood supply usually delivers an adequate amount of glucose, but if some regions of the brain become especially active, the cells located there consume the glucose faster than it can be supplied. In such cases, extra nutrients are supplied by astrocytes. Astrocytes maintain a small stock of nutrients in the form of glycogen, an insoluble carbohydrate that is also stocked by the liver and the muscles. The metabolism of glycogen causes increase in the levels of adenosine, a neuromodulator that has inhibitory effects. This accumulation of adenosine increases the amount of delta activity during the next nightís sleep. The cells in that region rest, and the astrocytes renew their stock of glycogen. Investigators found that when they administer a drug that stimulates adenosine receptors, they saw increases in delta activity during the animalsí slow-wave sleep.
Neural Control of Arousal
Sleep is not a unitary condition but consists of several different stages with very different characteristics. Wakefulness, too, is nonuniform; sometimes we are alert and attentive, and sometimes we fail to notice much about what is happening around us. Sleepiness has an effect on wakefulness; if we are fighting to stay awake, the struggle might impair our ability to concentrate on other things. But everyday observations suggest that even when we are not sleepy, our alertness can vary.
Experimental evidence suggests that the brain stem contains circuits of neurons that can increase an animalís level of alertness and activation-what is commonly referred to as arousal. In 1949, Moruzzi and Magoun found that electrical stimulation of the brain stem reticular formation produced arousal. The reticular formation, which occupies the central core of the brain stem, receives collateral axons from ascending sensory pathways. Presumably, sensory input, the event that normally produces arousal, activates the reticular formation by means of these collateral axons. The activated reticular formation then arouses the cerebral cortex by means of two pathways. The dorsal pathway projects to the medial and intralaminar nuclei of the thalamus, which in turn projects to the cerebral cortex: and the ventral pathway projects to the lateral hypothalamus, basal ganglia, and basal forebrain region. One part of the basal forebrain region projects extensively to the cerebral cortex, and another part projects to the hippocampus.
At least three different systems of neurons play a role in some aspect of arousal and wakefulness: noradrenergic, acetylcholinergic, and serotonergic. Investigators have long known that catecholamine agonists such as amphetamine produce arousal and sleeplessness. These effects appear to be mediated primarily by the noradrenergic system of the locus coeruleus, located in the dorsal pons. Neurons of the locus coeruleus send axons that branch widely , releasing norepinephrine (from axonal varicosities) throughout the neocortex, hippocampus, thalamus, cerebellar cortex, pons, and medulla; thus, they potentially affect widespread and important regions of the brain.
Adenosine Ė a chemical produced when increased neural activity requires the breakdown of glycogen stored in astrocytes; may increase delta activity during the next nightís sleep and thus enable the region to recover from its energy expenditure.
Locus coeruleus [ sa roo lee us]- a dark-colored group of noradrenergic cell bodies located in the pons near rostral end of the floor of the fourth ventricle; involved in arousal and vigilance.
The rate of firing of neurons in the locus coeruleus falls almost to zero during REM sleep and increases dramatically when the animal wakes.
The second neurotransmittter involved in arousal is acetylcholine. Two groups of acetylcholinergic neurons, one in the pons and one located in the basal forebrain, produce activation and cortical desynchrony when they are stimulated. Researchers have long known that acetylcholinergic agonists increase them. Microdialysis probes were used to measure the release of acetylcholine in the striatum, hippocampus, and frontal cortex- three regions whose activity is closely realted to an animalís alertness and behavioral arousal. They found that the levels of Ach in these regions were closely related to the animalís level of activity. In addition electricallly stimulated a region of the pontine reticular formation found that the stimulation activated the cerebral cortex and increased the release of acetylcholine there by 350 percent.
A third neurotransmitter, serotonin (5-HT), also appears to play a role in activating behavior. Almost all of the brainís serotonergic neurons are found in the raphe nuclei, which are located in the medullary and pontine regions of the reticular formation. The axons of these neurons project to many parts of the brain, including the thalamus, hypothalamus, and neocortex. Stimulation of the raphe nuclei causes locomotion and cortical arousal (as measured by the EEG), whereas PCPA, a drug that prevents the synthesis of serotonin, reduces cortical arousal.
Raphe nuclei [ruh fay] Ė a group of nuclei located in the reticular formation of the medullla, pons, and midbrain, situated along the midline; contain serotonergic neurons.
Neural Control of Slow-Wave Sleep
Although sleep is a behavior that involves most of the brain, one region seems to be particularly important: the basal forebrain region, located just rostral to the hypothalamus. Found that destruction of this area produced total insomnia in rats. The animals subsequently fell into a coma and died.
Basal forebrain region- the region at the base of the forebrain rostral to the hypothalamus; involved in thermoregulation and control of sleep.
The effects of these lesion experiments are corroborated by the effects of electrical stimulation of the basal forebrain region. Found that electrical stimulation produced signs of drowsiness in the behavior and the EEG of unanesthetized, freely moving cats.
A considerable amount of evidence suggests that forebrain mechanisms involved in sleep are closely linked to those involved in thermoregulation Ėan animalís ability to regulate its body temperature. Part of the basal forebrain, the preoptic area and the adjacent anterior hypothalamus (often referred to as the POAH), contains neurons involved in thermoregulation. Some of these neurons are directly sensitive to changes in brain temperature, and some receive information from thermosensors located in the skin. Warming of the POAH, like electrical stimulation, induces slow-wave sleep. Thus, a more "natural" stimulation mimics the effects of electrical stimulation. In addition, many neurons in the POAH increase their rate of firing when the animal falls asleep, and most of them also do so in response to increases in body temperature. The excessive sleepiness that accompanies a fever may be produced by this mechanism. And perhaps the connections between the thermosensors in the skin and the POAH account for the drowsiness and lassitude we feel on a hot day.
The most likely function of slow-wave sleep is to permit the brain to rest.
POAH- the region of the preoptic area and the adjacent anterior hypothalamus, involved in thermoregulation and induction of slow-wave sleep.
Neural Control of REM Sleep
REM sleep consists of desynchronized EEG activity, muscular paralysis, rapid eye movements, and increased genital activity. The rate to cerebral metabolism is as high as it is during waking. In laboratory animals, REM sleep also includes PGO waves. PGO waves (for pons, geniculate, and occipital). They consist of brief, phasic bursts of electrical activity that originate in the pons and are propagated to the lateral geniculate nuclei and the to the primary visual cortex. The first sign of an impending bout of REM sleep is the presence of PGO waves- in this case, recorded from electrodes implanted in the lateral geniculate nucleus.
As we shall see, REM sleep is controlled by mechanisms located within the pons. The executive mechanism consists of a group of neurons that secrete acetylcholine. During waking and slow-wave sleep, REM sleep is inhibited by the serotonergic neurons of the raphe nuclei and the noradrenergic neurons of the locus coeruleus.
PGO wave- bursts of phasic electrical activity originating in the pons, followed by activity in the lateral geniculate nucleus and visual cortex; a characteristic of Rem sleep.
The Executive Mechanism
Researchers have long known that acetylcholinergic agonists facilitate REM sleep.
The brain contains several groups of acetylcholinergic neurons. The ones that play the most central role in triggering the onset of REM sllep are found in the dorsolateral pons, primarily in the pedunculopontine tegmental nucleus (PPT) and laterodorsal tegmental nucleus (LDT).
Peribrachial area- the region around the brachium conjunctivum, located in the dorsolateral pons; contains acetylcholinergic neurons involved in the initiation of REM sleep.
Several studies shown that the activity of single neurons in the peribrachial area is related to the sleep cycle. Most of these neurons fire at a high rate during REM sleep or during both REM sleep and active wakefulness.
Where do the acetylcholinergic neurons of the peribrachial area exert their effects? the axons of these neurons project to the medial pontine reticular formation; to several regions of the forebrain, including the thalamus, basal ganglia, preoptic area, hippocampus, hypothalamus, and cingulate cortex; and to several brain stem regions involved with the control of eye movements.
If a small amount of carbachol, a drug that stimulates acetylcholine receptors, is infused into the medial pontine reticular formation (MPRF), the animal will display some or all of the components of REM sleep. Carbachol is effective when infused into the MPRF because it stimulates postsynaptic acetylcholine receptors of neurons that receive projections from the Ach cells of the peribrachial area.
If the acetylcholinergic neurons in the peribrachial area of the pons are responsible for the onset of REM sleep, how do they control each of its components: cortical arousal, PGO waves, rapid eye movemnets, and muscular paralysis? As we saw, the acetylcholinergic neurons of the pons compromise an integral part of the reticular activating system. Axons to glutamatergic neurons in the mesopontine reticular formation, which, in turn, send axons to the acetylcholinergic neurons of the basal forebrain. Activation of the forebrain neurons produces arousal and cortical desynchrony. PGO waves appear to be controlled by direct connections between the peribrachial area and the lateral geniculate nucleus.
A recent PET study with human vounteers obtained some interesting results that may be related to dreaming. They found that during REM sleep, neural activity increased significantly in the ventral stream of the visual association cortex-the region of the brain involved in analysis of visual shapes.
The last of the REM-related phenomenon, muscular paralysis, is particularly interesting. As we will see, some patients with lesions in the brain stem fail to become paralyzed during REM sleep and thus act out their dreams. The same thing happens to cats- that is, assuming that they dream.
Carbachol-a drug that stimulates acetylcholine receptors.
Medial pontine reticular formation(MPRF)- a region that contains neurons involved in the initiation of REM sleep; activated by acetylcholinergic neurons of the peribrachial area.
Jouvetís lesions destroyed a set of neurons responsible for the muscular paralysis that occurs during REM sleep. These neurons, which are activated by nonacetylcholinergic neurons, are located just ventral to the locus coeruleus- in the subcoerulear region. Their axons travel caudally to the magnocellular nucleus, located in the medial medulla. Neurons in the magnocellular nucleaus send axonsto the spinal cord, where they form inhibitory synapses with motor neurons.
Magnocellular nucleus- a nucleus in the medulla; involved in the atonia (muscular paralysis) that accompanies REM sleep.
Inhibitory Effects of Serotonin and Norepinephrine
Serotonergic and noradrenergic agonists have inhibitory effects on REM sleep.
The fact that the amount of sleep is regulated suggests that sleep-promoting substances (produced during wakefulness) or wakefulness-promoting substances (produced during sleep) may exist. The sleeping pattern of the dolphin brain suggests that such substances do not accumulate in the blood. They may accumulate in the brain , but so far attempts to find them have not been successful. One hypothesis suggests that adenosine, released when neurons are obliged to utilize the supply of glycogen stored in astrocytes, serves as the link between increased brain metabolism and the necessity of sleep.
Three systems of neurons appear to be important for alert, active wakefulness: the noradrenergic system of the locus coeruleus, the acetylcholinergic system of the peribrachial area of the pons and the basal forebrain, and the serotonergic system of the raphe nuclei.
Slow-wave sleep occurs when neurons in the basal forebrain become active. These neurons are also sensitive to changes in temperature, leading some investigators to suggest that an important function of slow-wave sleep is to lower brain temperature (and permit the brain to rest). REM sleep occurs when the activity as acetylcholinergic neurons in the peribrachial area increases. These neurons initiate PGO waves and cortical arousal through their connections with the thalamus, and they activate neurons in the MPRF whose axons travel to the acetylcholinergic neurons of the basal forebrain. The peribrachial neurons also produced rapid eye movements. Atonia (muscular paralysis that prevents our acting out our dreams) is produced by a group of acetylcholinergic neurons located in the magnocellular nucleus of the medulla, which in turn produce inhibition of motor neurons in the spinal cord. REM sleep, too is related to temperature; it occurs only after the brain temperature has been lowered by a period of slow-wave sleep.
The noradrenergic neurons of the locus coeruleus and the serotonergic neurons of the raphe nuclei have inhibitory effects on pontine neurons responsible for REM sleep. Bouts of REM sleep begin only after the activity of the noradrenergic and serotonergic neurons ceases; whether this event is the only one to trigger REM sleep or whether direct excitation of acetylcholinergic neurons also occurs is not yet known.
DISORDERS OF SLEEP
Problems Associated with REM Sleep
Problems Associated with Slow-Wave Sleep
Drug dependency insomnia An insomnia caused by the side effects of ever-increasing doses of sleep medications.
Sleep apnea [app nee a] Cessation of breathing while sleeping.
Problems Associated with REM Sleep
Narcolepsy [nahr ko lep see] A sleep disorder characterized by periods of irresistible sleep, attacks of cataplexy, sleep paralysis, and hypnagogic hallucinations.
Sleep attack A symptom of narcolepsy; an irresistible urge to sleep during the day, after which the person awakes feeling refreshed.
Cataplexy [kat a plex ee] A symptom of narcolepsy; complete paralysis that occurs during wake.
Sleep paralysis A symptom of narcolepsy; paralysis occurring just before a person falls asleep.
Hypnagogic hallucination [hip na gah jik] A symptom of narcolepsy; vivid dreams that occur just before a person falls asleep; accompanied by sleep paralysis.
Problems Associated with Slow-Wave Sleep
REM without atonia [ ay tone ee a] A neurological disorder in which the person does not become paralyzed during REM sleep and thus acts out dreams.
Although many people believe that they have insomnia-that they do not obtain as much sleep as they would like-insomnia is not a disease. Insomnia can be caused by depression, pain, illness, or even excited anticipation of a pleasurable event. Far too many people receive sleeping medications, which often lead to a condition called drug dependency insomnia. Sometimes, insomnia is caused by sleep apnea, which can often be corrected surgically or treated by wearing a mask that delivers pressurized air.
Narcolepsy is characterized by four symptoms. Sleep attacks consists of overwhelming urges to sleep for a few minutes. Cataplexy is sudden paralysis, during which the person remains conscious. Sleep paralysis is similar to cataplexy, but it occurs just before sleep or on waking. Hypnagogic hallucinations are dreams that occur during periods of sleep paralysis, just before a nightís sleep. Sleep attacks are treated with stimulants such as amphetamine, and the other symptoms are treated with serotonin agonists. Studies with narcoleptic dogs suggest that the disorder associated with REM sleep, REM without atonia, is a genetic disorder that can also be produced by damage to brain stem mechanisms that produce paralysis during REM sleep.
During slow-wave sleep, especially during stage 4, some people are afflicted by bed-wetting (nocturnal enuresis), sleepwalking (somnambulism), or night terrors. These problems are most common in children, who usually outgrow them. Only if they occur in adults do they suggest the existence of a physical or psychological disorder.
Circadian Rhythms and Zeitgebers
Circadian rhythm [sur kay dee un or sur ka dee un] A daily rhythmical change in behavior or physiological process.
Zeitgeber [tsite gay ber] A stimulus (usually the light of dawn) that resets the biological clock responsible for circadian rhythms.
Role of Suprachiasmatic Nucleus
Suprachiasmatic nucleus (SCN) [soo pra ky az mat ik] A nucleus situated atop the optic chiasm. It contains a biological clock responsible for organizing many of the bodyís circadian rhythms.
The Nature of the Clock
Control of Seasonal Rhythms: The Pineal Gland and Melatonin
Pineal Gland [py nee ul] A gland attached to the dorsal tectum; produces melatonin and plays a role in circadian and seasonal rhythms.
Melatonin [mell a tone in] A hormone secreted during the night by the pineal body; plays a role in circadian and seasonal rhythms.
Changes in Circadian Rhythms: Shift Work and Jet Lag.
Our daily lives are characterized by cycles in physical activity, sleep, body temperature, secretion of hormones, and many other physiological changes. Circadian rhythms-those with a period of approximately one day- are controlled by biological clocks in the brain. The principal biological clock appears to be located in the suprachiasmatic nuclei of the hypothalamus; lesions of these nuclei disrupt most circadian rhythms, and the activity of neurons located there correlates with the day-night cycle. Light serves as a zeitgeberfor most circadian rhythms. That is, the biological clocks tend to run a bit slow, with a period of approximately 25 hours. The sight of sunlight in the morning is conveyed from the retina to the SCN-directly and via the IGL of the lateral geniculate nucleus. The effect of the light is to reset the clock to the start of a new cycle.
Individual neurons, rather than circuits of neurons, are responsible for the "ticks." Studies with tissue cultures suggest that synchronization of the firing patterns of individual neurons is accomplished by means of chemical communication between cells, perhaps involving astrocytes. In the fruit fly, two genes, tim and per, are responsible for circadian rhythms. These genesí proteins (TIM and PER) bind, travel to the nucleus, and inhibit further protein synthesis until they disintegrate and the cycle begins again.
The SCN and the pineal gland control annual rhythms. During the night the SCN signals the pineal gland to secrete melatonin. Prolonged melatonin secretion, which occurs during winter, causes animals to enter the winter phase of their annual cycle. Melatonin also appears to be involved in synchronizing circadian rhythms: The hormone can help people to adjust to the effects of shift work or jet lag and even synchronize the daily rhythms of blind people for whom light cannot serve as a zeitgeber.
A Physiological And Behavioral Description
Why Do We Sleep?
Physiological Mechanisms Of Sleep And Waking
Disorders Of Sleep
8. Circadian rhythms are largely under the control of a mechanism located in the suprachiasmatic nucleus. They are synchronized by the day-night light cycle.