SLEEP, DREAMING and CIRCADIAN RHYTHMS (CHAP 14)
Introduction to Circadian rhythms
Animals generate cyclic behaviors that are regulated by internal clocks.
However, we will see that these clocks can be reset or entrained by external stimuli, such as the cycle of day and night, or the tides.
Endogenous cycles are advantageous because they often anticipate external changes
Migration starts before winter
Birds in cages show migratory restlessness
Cycles can last about a year: circaannual:
Hibernation: bats, ground squirrels, hamsters.
Seasonal changes in reproduction, body fat
Cycles can last about a day: Circadian.
Sleeping and waking
Temperature changes
Hormonal changes, etc.
All these cycles stay in synchrony, suggesting that there is a Master Clock
Cycles are adapted to the movements of Earth.
SLEEP
The Physiological and Behavioral Events of Sleep.
The Three Standard Psychophysiological Measures of Sleep.
Data obtained by measuring:
1) The activity of the brain: electroencephalogram (EEG)
2) Movement of the eyes: electrooculogram (EOG)
3) Activity of neck muscles: electromiogram (EMG)
Stages of sleep
Sleep EEG (stages distinguished using EEG) (Fig. 14.2):
Alert wakefulness : Low amplitude, high frequency EEG waves: 13-30 Hz.
Just before sleep, bursts of alpha waves appear (8-12 Hz).
4 stages of sleep EEG:
STAGE 1 (Initial Stage 1):
Low amplitude waves, frequency slower than alert wakefulness.
STAGE 2:
Amplitude of waves increases and frequency slows down.
K complexes appear: single positive and negative wave.
Sleep spindles appear: 1-2 sec burst of 12-14 Hz waves.
STAGE 3:
Amplitude of waves increases and frequency slows down.
Delta waves appear occasionally: 1-2 Hz
STAGE 4:
Predominance of delta waves.
Stages 3 and 4 are also known as slow-wave sleep (SWS).
EMERGENT STAGE 1 EEG (ALSO CALLED REM SLEEP): Accompanied by:
REM (rapid eye movements)
Loss of muscle tone (Fig. 14.3)
REM Sleep and Dreaming
The observation that 80% of awakenings from REM sleep lead to dream recall provided evidence that REM sleep is the physiological correlate of dreaming.
Only 7% of awakenings from non REM sleep stages lead to dream recall.
Testing Common Beliefs about Dreaming.
1) External stimuli can become incorporated in dreams.
2) Dreams run on “real time”
3) People who claim that they do not dream report dreaming if awakened in REM
4) Sleeptalking and Sleepwaking (somnambulism), and enuresis (bedwetting) occur least frequently during REM sleep (core muscles are relaxed), and most frequently in Stage 4 sleep.
The Interpretation of Dreams
Do dreams represent repressed wishes?
Sigmund Freud: Dreams (manifest dreams) are disguised versions of our real dreams (latent dreams).
Interpretation of dreams was important for exposing latent dreams and cure the patients.
Hobson's Activation-synthesis theory: Information to the cortex is random and brain makes up a story to make sense of this stimulus.
The dream is embellished depending on the education, culture, abilities and tendencies of the subjects. Thus, dreams do tell something about dreamer.
Lucid Dreams.
Dreams in which the dreamer is aware that he/she is dreaming and can influence the course of the dreams. It is like being awake in a dream.
Web Link for Dreams (Lucid Dreaming, etc, etc, etc)
Why do we Sleep, and Why do we Sleep When we do?
We spend approximately 1/3 of our lives sleeping. Why? and what do we get in return? There are two theories about sleep.
1) RECUPARATION THEORY
Sleeps restores homeostasis. Repairs damage.
But, why would the Giant sloth need 20 hours? there is no good correlation between amount of energy spent and sleep time.
2) CIRCADIAN (EVOLUTIONARY) THEORY:
Sleep evolved for saving energy and protection. It is a cyclic behavior that results from an inernal timing mechanism that cannot be avoided.
There is good correlation between the time an animal needs to feed and how vulnerable it is during sleep. Example: Zebra (sleeps little), lion (sleeps a lot, FIG. 14.4).
Comparative analysis of Sleep.
Virtually all animals sleep, but the time spent varies widely among species (TABLE 14.1):
Giant sloth 20 hours
Cat, golden hamster 14
Gorilla 12
Chimpanzee 9
Humans 8 (babies: 18 hours)
Cow, sheep 3
Horse 2
The comparative analysis of sleep suggest the following conclusions:
1. The fact that all mammals and birds sleep suggest that sleep serves some important physiological function.
Even animals at high risk of predation sleep.
Other animals develop complex mechanisms for sleeping, e.g., dolphins sleep with only one hemisphere at a time so they can surface for air.
2. The fact that all mammals and birds sleep suggets that function of sleep is not some special higher-order human function.
3. The large variability in time spent sleeping among species suggests that although sleep may be essential for survival, it is not necessarily needed in large quantities.
4. There is no clear relationship between a species's sleep time and its level of activity, body size or body temperature.
This observation does not support the recuperation theory, but is consistent with the circadian theory, which predicts that sleep time is related to how vulnerable certain specias are, and how much time they need to satisfy other survival needs.
Circadian Sleep Cycles
The sleep-wake cycle is the most obvious circadian rhythm (lasting about a day), but many other physiological, biochemical, or behavioral processes also show circadian rhythmicity.
What keeps these behaviors coupled to a 24 hour cycle?
We will see that animals have internal timinig mechanisms known as biological clocks, and these are kept entrained to a precise 24-hour cycle by temporal cues in the environment, known as zeitgebers (time givers).
The most important of these cues, or zeitgebers, is the daily cycle of light and dark in each day. For marine animals, the tides function as zeitgebers.
Within certain limits, it is possible to lengthen or shorten the circadian cycles by adjusting the duration of light and dark periods. For instance, subjects begin to adjust to 10 hours of light and 10 hours of dark. But if the changes are greater, animals do not adjust to shorter or longer light-dark cycles.
Experiments in caves with artificial, 28-hour days: 9 hours of sleep and 19 active hours. Adjustment was poor, if at all. This suggests there will be problems for humans living in other planets.
Free-Running Circadian Sleep-Wake Cycles.
Without zeitgebers, animals display free-running rhythms, increasingly getting out of phase with 24-hour days (Fig. 14.5).
Examples: people living in caves, astronauts, some blind people.
The duration of each cycle is called free-running period, and these periods are longer than 24 hours, about 25 hours in most humans.
Thus, the biological clock runs are a bit slow, and it is entrained on a daily basis by the light-dark cycle, or other zeitgebers.
The fact that the lenght of free-running periods are maintained constant in spite day-to-day variations in physical and mental activities provides support for the circadian theory of sleep.
Jet Lag and Shift Work
Jet lag occurs when the zeitgebers are accelerated during east-bound flights (phase advances) or decelerated during wet-bound flights.
It is easier to adjust crossing time zones going west
There is phase delay: stay awake later and awaken later
Going east there is a phase advance: going to sleep sooner, awaken earlier
Traveling east results in temporary disadvantage
A study of major league baseball found that
teams going west won 44% of games
whereas teams going east won 37% of games
In Shift work, the zeitgbers stay the same, but workers are forced to change their sleep-wake cycles to meet the demands of changing schedules. These changes may result in large phase shifts.
Both Jet lag and Shift work often produce sleep disturbances, fatigue, general malaise, and deficits on tests of physical and cognitive abilities. Readjustment to jet lag can take up to 10 days for large phase changes.
Facilitating adjustment to jet lag and shift work.
For reducing jet lag:
Gradual shift of one's sleep-wake cycle in the days before the trip.
Light treatment early in the morning after east-bound flights facilitate the phase advance required for adjsutment.
Studies in hamsters suggest that a vigorous workout early in the morning may also help.
For reducing shift work:
Shifts to schedules that begin later in the day produce less disturbances because they require phase delay. It is easier to go to bed and get up later than the reverse.
Effects of Sleep Deprivation
The Recuperation theory (wakefulness has a debilitating effect) predicts:
1) Long periods of wakefulness will produce physiological and behavioral disturbances.
2) These disturbances will grow steadily as deprivation continues
3) The missed sleep will be regained
In contrast, the Circadian (evolutionary) theory predicts:
1) There will be no debilitating effect, except for tendency to fall asleep
2) Tendency to sleep will be during normal sleeping time
3) There will be little or no compensation for the loss of sleep.
Have these predictions been confirmed?
Two Classic Sleep-Deprivation Case Studies.
1. One study showed that the urge to sleep depends largely on the time of day, not just how recently you have slept.
If one stays awake, one will feel sleepy at night, but less so in the morning.
2. After being awake for 11 days, a subject slept only 14 hours the first night, and from then on only 8 hours.
Experimental Studies of Sleep Deprivation in Humans.
Moderate sleep deprivation (3-4 h) produce:
1. Increase in sleepiness
2. Disturbances of mood
3. Poor performance on test of vigilance (detecting a different tone in a series of tones)
2-3 days of sleep deprivation:
1. Subjects experience microsleeps (2-3 seconds), but remain sitting or standing. Microsleeps disrupt performance on vigilance tests.
Longer periods of deprivation (72 hours or more)
1. No effect on strength or motor performance were found
2. No effect on cognitive performance (IQ) was found
3. May affect creativity
COMPARE THESE RELATIVELY MINOR EFFECTS WITH DEPRIVATION OF FOOD, WATER, SEX, THAT HAVE MORE SERIOUS CONSEQUENCES.
Sleep-Deprivation Studies with Laboratory Animals.
Carousel experiment in rats (Fig. 14.7).
Experimental rat and joked control are wired for EEG to detect when rats fall asleep.
When experimental rats falls asleep, it is pushed into a shallow pond by a rotating disk, and the rat wakes up
It is difficult to rule out stress.
Experimental rats died after several days, and showed postmortem signs indicative of stress:
-gastric ulcers
-internal bleeding
-swollen adrenal glands
REM-Sleep Deprivation. What are the functions of REM sleep?
1. After deprivation, there tends to be more REM periods (Fig. 14.8).
2. Following REM-sleep deprivation, there is a REM rebound: subjects have more REM sleep in the following 2-3 nights (Fig. 14.8).
Interestingly, if REM is replaced by a similarly long period of wakefulness, there is no REM compensation, confirming idea that wakelfulness and REM sleep are equivalent in many ways.
What is therefore the function of REM?
Several possibilities have been suggested, but the issue is not clear. REM sleep may:
1. Maintain mental health
2. Maintain motivation
3. May be necessary for the processing of certain memories (consolidation)
There is some experimental support
However, certain tricyclic antidepressants (e.g., imipramine) can eliminate REM without serious consequences.
Sleep Deprivation Increases the Efficiency of Sleep.
Individuals who are deprived of sleep become more efficient sleepers.
They take less time to fall asleep
They have fewer interruptions of sleep
These subjects show a higher proportion of Slow Wave Sleep.
Although total sleep is not regained, stage 4 sleep tends to be regained, with corresponding reductions in stages 1 & 2.The idea that stage 4 may be specially important and restorative is supported by the fact that short sleepers have as much stage 4 sleep as long sleepers.
Also, waking up sleepers during stage 4 produces more sleepiness than waking them up during REM.
NOTE: because we can become more efficient sleepers, sleep deprivation studies are not useful for discovering how much humans need to sleep. For this, it is necessary to reduce sleep for many weeks to allow subjects to adapt. Only at this point one can assess how much sleep is really needed.
Four Areas of the Brain Involved in Sleep.
Two Areas of the Hypothalamus Involved in Sleep.
During WW I, von Economo observed the effects of encephalitis lethargica and proposed that:
the posterior hypothalamus promotes wakefulness,
the anterior hypothalamus promotes sleep (Fig. 14.9)
Reticular Activating System and Sleep.
In 1936, Bremer proposed that sleep is a passive consequence of a reduction in sensory input to the forebrain.
Cerveau isole preparation. He studied the effect of the cerveau isole preparation: the transection of the brainstem between superior and inferior colliculi (Fig. 14.10).
Animal showed continuos slow-wave sleep. Only strong visual or olfactory stimuli produced a desynhronized EEG for a brief time.
Reticular activating system theory of sleep
Encephale isole preparation. However, when Bremer sectioned the brainstem at a more caudal level (encephale isole preparation, Fig. 14.10) the normal cycles of sleep and wakefulness were not perturbed (even though sensory input was abolished as in the cerveau isole preparation).
This suggested that astructure that induced wakefulness was located between the cerveau isole and encephale isole cuts.
Later, it was proposed that this structure was the reticular formation in the brainstem: lack of activity in the reticular formation produces sleep and high activity produces wakefulness. This theory is known as the reticular activating system theory of sleep.
Reticular REM-Sleep Nuclei.
REM sleep is controlled by a variety of nuclei scattered throughout the caudal reticular formation (Fig. 14.11).
Each site is responsible for controling one of the major indices of REM sleep: reduction of core-muscle tone, EEG desynchronization, rapid eye movements, etc (Fig. 14.11).
THE CIRCADIAN CLOCK: Neural and Molecular Mechanisms.
The biological clock that controls the sleep-wake cycles in the absence of zeitgebers is called circadian clock.
The circadian clock is located in the suprachiasmatic nuclei (SCN), located in the medial hypothalamus, just above the optic chiasm. FIG. 14.12
Ciracadian cycles, including the sleep-wake cycles, are disrupted by lesions of the suprachiasmatic nucleus.
This nucleus shows cycles of electrical, metabolic, and biochemical activity, even when it is isolated from the rest of the brain by circular cuts.
Transplanting the SCN from mutant hamsters with 20-hour cycles (fetuses) to normal hamsters induced changes in the rhythms of the hosts.
Mechanisms of Entrainment.
How does the 24-hour light-dark cycle entrain the sleep-wake cycle and other circadian rhythms?
It was found that the suprachiasmatic nuclei receive input from the retina, through a pathway known as the Retinohypothalamic Tract.
If this retinal input is blocked, light cannot reset the biological clock (animal is in a free-running rhythm) FIG. 14.12.
This mechanismn works even in blind mole rats.
In blind subjects, there can be two conditions:
If the optic pathway is sectioned before it gets to the SCN, the subject will be blind and will be on a free-running cycle (the circadian clock does not receive light).
If the optic pathway is sectioned after the SCN, the subject will be blind, but the circadian cycle will be entrained to a 24-hour cycle (the clock receives light).
Interestingly, the photoreceptors that entrain the SCN are not the regular rods or cones, but a special class of ganglion cells that responds to light.
(Genetics of Circadian Rhythms. Not included)
Drugs that Affect Sleep.
1. Hypnotics.
Benzodiazepines (Valium, Librium)
Can cause tolerance to the drug and addiction
Long term use may disturb sleep patterns and lead to insomnia.
2. Antihypnotics.
Stimulants (cocaine, amphetamine)
Tricyclic antidepressants (e.g., imipramine)
They increase the activity of catecholamines:
Norepinephrine
Epinephrine
Dopamine
They can suppress REM sleep
3. Melatonin
It has been suggested that the SCN regulates the synthesis of the hormone melatonin from the neurotransmitter serotonin by the pineal gland, located under the posterior end of the corpus callosum (Fig. 14.13).
Melatonin increases sleepiness. Increased secretion of melatonin begins between 8-10 pm, and decreases during the day
Melatonin resets clock by acting on receptors of the SCN.
Melatonin pills administered during the day produce quicker and better sleep.
Can be used to shift phase of sleep cycle. Melatonin has opposite effect to those of bright light in shifting phase of sleep cycle.
Melatonin pills during day (before dusk) may help with east-bound flights (produce phase advance)
Melatonin pills early in the morning can help with adaptation to west-bound flights (produce phase delay)
Sleep Disorders.
1. Insomnia. Disorder of initiating or maintaining sleep.
Many cases of insomnia are iatrogenic (created by medical action).
Consequences of long term use of sleeping pills.Sleep apnea. The patient stops breathing many times each night.
peripheral causes: atonia and collapse of respiratory pathways
central causes: failure to keep breathing movements.
Restless leg syndrome. Uneasiness in the legs that prevents sleeping.
Nocturnal myoclonus. Periodic twitching of the legs and body leads to poor sleep.
Insomnia is not necessarily a problem of too little sleep, but it is often a problem of too little undisturbed sleep.
Most effective treatment is sleep restriction therapy.
In this therapy, the amount of time the insomniac is allowed in bed is substantially reduced, and then it is gradually extended as the patient improves.
2. Hypersomnia. Disorders of excessive sleep or sleepiness.
Narcolepsy (1 in 2000)
Narcoleptics usually sleep about an hour more than normals on average.
What characterizes them is:
1. Severe daytime sleepiness and repeated breef (15 min) periods of sleep
Falling asleep during activities (talking, doing sports, etc).2. Cataplexy: sudden loss of muscle tone
They can also show (occasionally also in normal individuals):
3. Sleep paralysis: inability to move when falling asleep or waking up
4. Hypnagogic hallucinations: dreamlike experiences during wakefulness
In normal subjects, a nucleus in the caudal reticular formation (nucleus magnocellularis) normally induces muscle relaxation during REM (Fig. 14.11).
Narcoleptic dogs. Studies in a strain of narcoleptic dogs has shown that this nucleus is also active during narcoleptic attacks, which would cause the collapse of the subjects during these attacks.
OREXIN. Studies in these dogs also revealed the genes associated with narcolepsy. These genes encode a receptor protein that binds a neuropeptide neurotransmitter called orexin. These dogs are deficient in this protein
Orexin is synthesized in the posterior hypothalamus, which promotes wakefulness.
In humans suffering from narcolepsy, the cause of narcolepsy appears to be a hereditary disorder that stimulates the immune system to attack and destroy orexin-secreting neurons. Symptoms typically appear during adolescence.
Interestingly, deficiencies in the orexin-binding protein are not only associated with narcolespy, but also with a decrease in eating behavior.
REM-Sleep-Related Disorders.
Patients that due to injury or other reasons do not have REM sleep are ofen not affected by lack of REM sleep.
Some patients experience REM sleep without core-muscle atonia, which is thought to prevent the acting out of dreams.
The effects of Long-Term Sleep reduction. How much sleep do we really need?
To answer this question, long term sleep deprivation studies are necessary to allow for changes in sleep efficiency.
Long-term reduction of nightly sleep
Associated with an increase in sleep efficiency.
Less time required for falling asleep, fewer awakenings, increases in stage 4 of SWS.After a year, most subjects were sleeping less than they had previously, with no excessive sleepiness.
Long-term reduction by napping
Monophasic sleep cycles (most adults) vs. polyphasic sleep cycles (babies)
Several studies have replicated the legend of Leonardo da Vinci: work 4 hours and nap for 15 minutes. This means only 1.5 hours of sleep a day! One can save a lot of time.
Help for getting a good night's sleep (not in exam )
Drugs:
Sleep-Eze, Sominex, Dormin:
Nonaddictive, over-the-counter antihistamines. May cause morning drowsiness.
Desyrel: A prescription antidepressant ideal for those who wake up frequently.
Herbal:
Valerian: with no addiction and no morning drowsiness, this bitter herb can be used to make tea, but it is easier to swallow as a pill.
Hops: Use in beers, it makes one drowsy. Available in teas and "hops drops".
Aromatherapy:
Chamomile, lavender, passion flower and lemon balm are commonly used in teas and lotions. They smell good, but it is not clear whether they actually work.
Melatonin: declines after adolescence.
Urban legends.
Warm milk: Milk contains a chemical precursor of melatonin, "nature's sleep aid"
Tennis ball: Sewn to the back of T shirts to prevent snoring