Physiology of sleep

Objectives:
1. Explain the difference between sleep and coma.
2. Define what is meant by NREM (non-rapid eye movement, SWS) and REM (rapid eye movement)
sleep.
3. Describe how NREM and REM sleep are distributed during a normal night sleep in the average
adult human
4. Describe the behavioral and autonomic features associated with NREM and REM sleep.
5. Describe how the EEG, as a physiological tool, is being used to delineate in which stage of sleep
(or wakefulness) a person is.
6. Appreciate how the total sleep duration and different sleep stages vary with different ages in
normal humans.
7. Describe the current theories about the neural basis of sleep.

References:
 Guyton and hall physiology textbook.
 435 Boys’ slides
 434’s Teamwork
 433’s Teamwork

Helpful videos:
 Step 1 USMLE - Normal Sleep and Sleep Disorders (Duration\ 11:01)
 Stages of Sleep - Sleep Cycles (Duration\ 2:28)

‫ فقط شامل‬،‫ الملف مبني على االوبجكتفز الموجودة بالستيودنت قايد فموب شامل لجميع المعلومات الموجودة بقايتن أو التيمات السابقة‬:‫مالحظة‬
.‫المعلومات الموجودة بساليدات الطالب‬

1: Explain the difference between sleep and coma.

Sleep and coma:
Sleep coma
A state of unconsciousness from which one can be A state of unconsciousness from which one cannot
aroused by a sensory or other stimulus. be aroused by sensory stimulation
It may also be defined as a normal, periodic,
inhibition of the reticular Activating system.

2: Define what is meant by NREM (non-rapid eye movement, SWS) and REM (rapid eye movement)
sleep.

1- Slow-wave sleep (NREM):

- Deep, restful type of sleep characterized by decrease in: peripheral vascular tone, blood
pressure, respiratory rate, and metabolic rate.
- In this type: EEG waves are generally of low frequency.
- Dreams can occur but they can’t be remembered “the consolidation of dream in a memory will
not occur”, nightmares may also occur.
 - Sleep thought - lacks vivid sensory and motor sensations, is more similar to daytime
thinking, and occurs during slow-wave sleep
- Raphe nuclei of the medulla and pons and the secretion of serotonin.

2- Rapid eye movement (REM):

- Neurons of the pons.
- Called: “paradoxical sleep” because the brain is quite active and skeletal muscles contraction
occur.
- Lasts: 5 to 30 minutes and repeats about 90 minutes’ intervals.
- It may be absent if the individual is extremely tired, but it eventually returns as the person
becomes more rested.
-
- On EEG: a low amplitude and a high frequency pattern.
- It has several important features:
 Dreaming occur and can be recalled “at least in part”. True dream - vivid, detailed
dreams consisting of sensory and motor sensations experienced during REM
 Muscle tone throughout the body “except eye muscles” is exceedingly depressed.
 Heart rate and respiration become irregular.
 Despite decreased muscle tone, muscle contraction occurs in addition to rapid eye
movement.
 Brain metabolism increased as much and 20% percent, and the EEG shows brain waves
that are characteristics of the waking state.

In summary, REM is not as restful as SWS and it is a type of sleep in which the brain is quite active, but
this brain:
1- Is not aware cut off the external world.
2- Its activity is not channeled into purposeful external motor activity.

3: Describe how NREM and REM sleep are distributed during a normal night sleep in the average adult
human.
Distribution of sleep stages:
Enters
 While SWS occupies most of the total night sleep time (around 75- NREM
sleep
80%), it is interrupted by intervening1 REM sleep periods,
REM
approximately every 90 minutes. sleep This cycle is Stage I
 In a typical night of sleep: repeated at intervals
of about 90 minutes
- A young adult first enters NREM sleep, passes through stages throughout the 8
1, 2, 3 and 4 SWS, and then, 60-100 minutes from sleep hours or so of a
onset, goes into the first REM sleep episode. Stage IV
night sleep.
Stage II
- This cycle is repeated at intervals of about 90 minutes
throughout the 8 hours or so of a night sleep.
Stage III
- Therefore, there are 4-6 sleep cycles per night (and 4-6
REM periods per night).

1
Occur in time between events.
 - As the night goes on  there is progressive reduction in stages 3 and 4 sleep and
progressive increase in REM sleep.

 In a young adult SWS (NREM sleep) occupies 75-80% of a night sleep time, & REM sleep occupies 20-
25 % of the sleep time.

 REM sleep occupies 80 % of total sleep time in premature infants, and 50 % in full-term neonates.
 Thereafter, the proportion of REM sleep falls rapidly and plateaus at about 25% until it falls further in
old age.
 Children have more total sleep time and stage 4 sleep than adults.

4: Describe the behavioral and autonomic features associated with NREM and REM sleep.
Physiological changes during sleep:
 CVS: Pulse Rate, cardiac output, blood pressure, and vasomotor tone are decreased but the
blood volume is increased.
 Respiration: Tidal volume and rate of respiration is decreased. BMR is decreased 10-15%.
 Urine volume: Urine volume is decreased.
 Secretions: Salivary / lacrimal secretions are reduced; gastric/sweet secretions are increased.

5: Describe how the EEG, as a physiological tool, is being used to delineate in which stage of sleep (or
wakefulness) a person is.

EEG (electroencephalogram) waves:

Alpha A smooth electrical activity of Generally associated with a

waves 8 – 12 Hz recorded from the state of relaxation.
activity: brain. “awake but rested”

Beta Irregular electrical activity of Generally associated with a

waves 13 – 30 Hz recorded from the state of arousal.
activity: brain

Theta EEG activity of 3.5 – 7.5 Hz. Occurs intermittently

waves during early stages of slow
activity: wave sleep and REM sleep.

Delta Regular, synchronous occurs during the deepest

waves electrical activity of less than 4 stages of slow-wave sleep.
activity: Hz recorded from the brain. “deep sleep + infants +
organic brain disease”
 Sleep Classification is Based on EEG Features:
(A) NREM Sleep (SWS) :
 is divided into 4 stages:
1. Stage 1 NREM  when a person is initially falling asleep. Characterized by low-amplitude,
fast activity. Alpha waves diminish and Theta waves appear on EEG.
2. Stage 2 NREM  This is the first stage of true sleep.
Marked by appearance of Sleep Spindles. These are bursts of alpha-like 10-14z , 50 uV
waves .
3. Stage 3 NREM  Lower frequency (mainly theta), higher amplitude EEG waves. Body
temperature begin to fall. B.P decreases. Difficult to awaken the person. This stage occurs
about 20-25 minutes after falling asleep.
4. Stage 4 NREM  Still slower frequency (mainly delta) & still higher amplitude waves. The
difference is that the dreams in slow wave sleep are not remembered but in REM, dreams
can be remembered.
(B) REM Sleep:
Low-voltage, fast activity.

Stages of sleep “from 434 and 433”

REM Stage 1 Stage 2 Stage 3&4
Experience: Very active stage of Falling asleep and Base line of sleep Deep sleep.
dream. transition stage
Vivid dreams can between waking &
occur. sleep.
Duration: 20-25% of normal 1-5 minutes. - 90 minute. - 15-30 minutes.
night sleep. ~2.5% of a normal - ~45-60% of a - ~40% of all sleep.
night sleep. normal night sleep.
Signs: - Eye begins to roll - Slowing of heart rate, breathing
slightly. rate, and brain activity.
Waveform: Irregular, low-voltage Irregular, jagged, - EEG recording of slow, large
and fast activity. low voltage wave. amplitude wave.
- Sleep spindles. - Highly synchronized neuronal
- K-complex. activity.

Beta waves Alpha waves - stage 3  mainly theta.

- stage 4  mainly delta.
Notes: Length of rem stages - Start when sleep - Stages 3&4 sleep predominance
increases as the night has just begun, in the night, and length will
progresses. - Brain activity increase as night progress.
begins to decline.

*To remember the brain waves: “buying a tiny dog”.

6: Appreciate how the total sleep duration and different sleep stages vary with different ages in
normal humans.

Normal sleep cycle at different ages:

 Rem sleep is indicated in red.
 In a typical night of sleep, a young adult first enters NREM sleep
 passes through stages 1&2, and spends 70-100 min in stages
3&4  sleep the lightens, and a REM period follows.

 REM sleep occupies:

Premature infants 80% of total sleep. in a young adult
Full-term neonates 50% of total sleep. 15 - 20 hours. 6-9 hours.

Elderly 20% of total sleep. “from 20-69ys”

5-6 hours. NREM REM
75-80% 20-25%
Children More sleep time and stage 4 than adults.
10 -15 hours

*Note: this topic is present in the guide’s objectives and in both 433’s and 434’s teamwork but not in the boys’
slides.

7: Describe the current theories about the neural basis of sleep.

Theories of Sleep:
Although several theories of sleep have been proposed, most current evidence is in favor of the following:
(1) Serotonin, produced by the Raphe Nuclei, induces SWS sleep. The mechanism that triggers
REM sleep is located in the Pontine Reticular Formation; & the Ponto-Geniculo-Occipital circuit is
instrumental in generation of REM sleep.
(3) The hormone Melatonin (released from the Pineal Gland) plays an important role in day-night
entrainment of sleep.

Role of Serotonin & Melatonin in SWS:

 Raphe nucleus:
o Stimulation of Raphe Nuclei (which are situated in the lower pons & medulla) induces
SW.
o Destruction of the Raphe Nuclei makes the animal sleepless for several days until it dies.
 Administration of drugs that block serotonin formation make the animal sleepless for several
days.
 Transecting the brainstem at the level of the mid pons, leaves the animal in a state of
intense wakefulness for a period of days.
o The above-mentioned transection cuts the nerves going from the inhibitory serotonin-
secreting Raphe Nuclei to the Bulboreticular Facilitory Area of the RAS.
 o What does this mean? It means that the serotonin-secreting Raphe fibers normally
inhibit the Bulboreticular Facilitory Area to produce sleep.
 Injections of melatonin induce sleep.
 Stimulation of the Supra-chiasmal Nucleus (SCN) of hypothalamus by light falling on the
retina inhibits Melatonin release from Pineal gland  produces wakefulness.

Melatonin as a Circadian Controller of Sleep-Wake Cycles:

 Alternating “Sleep-Wake Cycles” are under marked Circadian Control.
 “Circadian Control/Rhythm”: means regulation of a biological rhythm (e.g. sleep-
wakefulness, hormone secretion , etc ) by day-night cycles .
 Darkness (e.g., at night) stimulates the Pineal Gland to secrete the hormone melatonin.
 Melatonin inhibits the RAS & thereby induces SWS.
 Daylight falling on the retina stimulates the Suprachiasmal Nucleus (SCN) of hypothalamus 
SCN inhibits melatonin secretion by the Pineal Gland, & thereby it inhibits sleep and promotes
wakefulness.

In Boys’ slides but not in the objectives!

Why Do We Sleep?
 Proximate Explanation:
– Because we begin to “feel” tired..melatonin 
– Need to consolidate energy and experiences.
– Need to avoid predators.
– Need to restore body cells and promote protein anabolism;
– Maintain hormonal secretions, immune function.
 Ultimate Explanation:
– sustains our ability to reproduce successfully, by maintaining good health.

Awake: This is the state of readiness / alertness and ability to react consciously to various stimuli.

DREAMS AND REMS

 What are true dreams for?
Although research has yet to answer this question, a prevalent view today is that dreams don’t
serve any purpose at all, but are side effects of REM.
To exercise groups of neurons during sleep some are in perceptual and motor areas REM occurs in
other mammals and to a much greater extent in fetuses and infants than adults REM sleep may
help consolidate memories.
 Disorders of Sleep:
 Insomnia (habitual sleeplessness; inability to sleep.)
• Reported to affect approximately 25% of the population occasionally, and 9% regularly.
• There appears to be no single definition of insomnia.
• One of the most important causes of insomnia seems to be sleeping medication.
• Insomnia is not a disease, but rather may be a symptom of pain, discomfort, or other
physical ailment.
 Drug dependency insomnia:
• An insomnia caused by the side effects of ever increasing doses of sleeping medications.
 Sleep apnea:
• Cessation of breathing while sleeping.
• Disorders of Sleep
 Narcolepsy:
• A sleep disorder characterized by periods of irresistible sleep, attacks of cataplexy, sleep
paralysis, and hypnagogic hallucinations.
o Sleep attack:
 A symptom of narcolepsy; an irresistible urge to sleep during the day, after
which the person awakes feeling refreshed.
o Cataplexy:
 A symptom of narcolepsy; complete paralysis that occurs during waking.
o Sleep paralysis:
 A symptom of narcolepsy; paralysis occurring just before a person falls
asleep.
o Hypnagogic hallucination:
 A symptom of narcolepsy; vivid dreams that occur just before a person falls
asleep; accompanied by sleep paralysis.
o REM sleep behavior:
 A neurological disorder in which the person does not become paralyzed
during REM sleep and thus acts out dreams.

Physiological Mechanisms of Sleep and Waking :

Neural Control of Arousal

Acetylcholine: - One of the most important neurotransmitters involved in arousal.
- Two groups of acetyl cholinergic neurons located in the pons and basal forebrain,
produce activation and cortical desynchrony when they are stimulated.
Norepinephrine: Catecholamine agonists produce arousal and sleeplessness; effects appear to be
mediated by the locus coeruleus in the dorsal pons.

Locus ceoruleus: A dark-colored group of noradrenergic cell bodies located in the pons near the rostral
end of the floor of the fourth ventricle; involved in arousal and vigilance.
 Serotonin (5-HT): Appears to play a role in activating behavior; almost all of the brain’s serotonergic
neurons are found in the raphe nucleus, located in the medullary and pontine regions
of the brain.
Raphe nucleus: A group of nuclei located in the reticular formation of the medulla, pons, and midbrain,
situated along the midline; contain serotonergic neurons.
Histamine A neurotransmitter implicated in control of wakefulness and arousal; a compound
synthesized from histidine, an amino acid.
Tuberomammillary A nucleus in the ventral posterior hypothalamus, just rostral to the mammillary bodies;
nucleus contains histaminergic neurons involved in cortical activation and behavioral arousal.

Hypocretin A peptide also known as orexin, produced by neurons whose cell bodies are located in
the hypothalamus; their destruction causes narcolepsy.
Neural Control of Slow-Wave Sleep
Ventrolateral - A group of GABAergic neurons in the preoptic area whose activity suppresses
preoptic area alertness and behavioral arousal and promotes sleep.
(VLPA):
- Destruction of this area has been reporter to result in total insomnia, coma, and
eventual death in rats.
Neural Control of REM sleep
PGO wave Bursts of phasic electrical activity originating in the pons, followed by activity in the
(Pontine, lateral geniculate nucleus and visual cortex, a characteristic of REM sleep.
Geniculate,
Occipital):

The Executive Mechanism

Peribrachial area The region around the brachium conjunctivum, located in the dorsolateral pons;
contains acetyl cholinergic neurons involved in the initiation of REM sleep.

Carbachol A drug that stimulates acetylcholine receptors

Medial pontine A region that contains neurons involved in the initiation of REM sleep; activated by
reticular formation acetyl cholinergic neurons of the peribrachial area.
(MPRF):

Magnocellular A nucleus in the medulla; involved in the atonia (muscular paralysis) that accompanies
nucleus: REM sleep.
 Biological Clocks
Suprachiasmatic A nucleus situated atop the optic chiasm. It contains a biological clock responsible for
nucleus organizing many of the body’s circadian rhythms
Melanopsin A photopigment present in ganglion cells in the retina whose axons transmit
information to the SCN, the thalamus, and the olivary pretectal nucleus.
Intergeniculate A part of the lateral geniculate nucleus that receives information from the retina and
leaflet (IGL): projects to the SCN; terminals release neuropeptide Y at the SCN.

Done by: Shahad AlEnezi.

.‫ وإن أسأت أو أخطأت فمن نفسي والشيطان‬،‫إن احسنت فمن هللا عز وجل‬