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Physiology of sleep Editing File
 Objectives:
1 Explain the difference between sleep and coma.

2 Define 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 EEG, as a physiological tool, is being used to delineate in which stage of sleep (or
wakefulness) a person is.

6 Describe Physiology of Sleep and EEG.

Appreciate how the total sleep duration and different sleep stages vary with different ages in
7
normal humans.
8 Describe the current theories about the neural basis of sleep.
 What is sleep? Why do we sleep? Female slides
Sleep theory #1: To rest,
Sleep: This is the state of unconsciousness from
- to gain relief from a hyperactive state
which a subject can be aroused by appropriate
sensory or other stimuli. Sleep theory #2: To heal,
- Sleep may also be defined as a normal, periodic, - Sleep also allows us to heal our bodies ; by helping the
inhibition of the reticular Activating immune system (our ability to fight disease), sleep
system(RAS). deprivation affect our metabolism(our internal
chemical reactions) , it may also help us save energy for
when we most need it
Coma: This is the state of unconsciousness from
which a person cannot be aroused by any external Sleep theory #3: To learn,
stimuli. - sleep may help the human brain get better organized
by filing away important memories and discarding
Awake: This is the State of readiness/alertness & ability unwanted information.
to react consciously to various \ any stimuli.
Sleep theory #4: To Dream,
The difference between coma and sleep is that in coma - Dreaming appears to be a by-product of REM sleep. So is
no external or internal stimuli can wake you up. it possible that the main reason why we sleep is to
dream? If so, why do we dream?

● Ultimate goal: Sustains our ability to reproduce successfully, by maintaining good health.
 Male slides
Sleep: introduction Functions of sleep
● Transitions between sleep and wakefulness
manifest a circadian rhythm consisting of an
1 Neural maturation.
average of 6–8 h of sleep and 16–18 h of
wakefulness.
2 Facilitation of learning, memory.
● Nuclei in both the brainstem and
hypothalamus are critical for the transitions
between states of consciousness. 3 Cognition.

● The brainstem ascending arousal system is Clearance of metabolic waste products generated by
comprised of groups of neurons that release 4
neural activity in the awake brain.
norepinephrine, serotonin, acetylcholine, or
histamine. 5 Conservation of metabolic energy.

6 Restore natural balances among the neuronal

centers.
Theories of sleep
Preservation and protection
Restoration theory
theory
-Body wears out during the day and sleep is -Sleep preserve energy and it provides
necessary to put it back in shape \ normal protection \ activity.
physiological condition.

-this is supported by findings that many of -for example, both body temperature and
the major restorative functions in the body caloric demand decrease during sleep,
like muscle growth, tissue repair, protein as compared to wakefulness.
synthesis, and growth hormone release
occur mostly, or in some cases only, during
sleep.
-This theory has studied from animals.
‫اﻟﻲ ﯾدﺧﻠون ﻓﻲ ﺑﯾﺎت ﺷﺗوي ﻋﺷﺎن ﯾﺣﻔظون طﺎﻗﺗﮭم‬
 Sleep: Mechanism
Male slides

Stimulation of some specific Sleep is promoted by a

Sleep is caused by an Active areas of the brain can complex set of neural and
Inhibitory Process. produce sleep: chemical mechanisms:
- Early theory of sleep: ● Raphe nuclei in the ● Daily rhythm of sleep and
The excitatory areas of the medulla oblongata: fibers arousal suprachiasmatic
upper brain stem, the from these raphe neurons nucleus of hypothalamus.
reticular activating system, secrete serotonin. ● Pineal glands secretion of
simply became fatigue during ● Drugs that blocks the melatonin (increased
the day activities, waking day formation of serotonin melatonin makes you sleepy).
and became inactive as a administered to an animal, ● Slow-wave sleep: Raphe
result. the animal cannot sleep for nuclei of the medulla and pons,
- Current theory: the secretion of serotonin
the next several days.
Sleep is caused by an active associated with initiation of
Serotonin is associated with
sleep.
inhibitory process the production of sleep.
● REM sleep: Neuron of pons.
Cont…
Male slides
Consists of two
parts:

Mesencephalic part: Thalamic part

Composed of area of grey matter Consists of grey matter in the thalamus.

When the thalamic part is stimulated, it
of midbrain and pons when this
develop activity in the cerebral cortex.
area is stimulated, nerve impulses
Thalamic part causes arousal that is
going to thalamus and disperse to
awakening from deep sleep (sensory input,
the cerebral cortex. pain, light).
This greatly affects the cortical The RAS and cerebral cortex continue to
activity. Mesencephalic part activate each other through a feedback
causes consciousness. system. the RAS also has a feedback
system with the spinal cord.
 Humans (normal sleep durations)

Age group Duration

New born 15-20 hours

Children 10-15 hours
Adults 6-9 hours
Old age 5-6 hours

Polysomnography “sleep study”:

Is a test used to diagnose sleep disorders,
polysomnography records your brain waves, the oxygen level
in your blood, heart rate and breathing as well as eye and leg
movements during the study
 REM (Rapid eye movement) sleep

Sleep Classification
NREM (NON rapid eye
movement)-(SWS) slow wave sleep

There are two types of sleep:

1. Non Rapid Eye Movement Sleep [Slow Wave Sleep- Dreamless] Note: Most sleep during each night is
of a slow wave Lasts for 80-90
- EEG waves are generally of low frequency . minutes.
- (NREM) sleep is not associated with rapid eye movements . Dreams / nightmare even occur.
2. Rapid eye movement sleep [Dreamful]. The difference is that the dreams in
- this type of sleep rapid eye movements occur (Neurons of the pons) slow wave sleep are not
remembered but in REM, dreams can
Dr.: NREM has 4 stages while REM has 1 be remembered.
Both types alternate with each other. stage. To sum up , the total stages of
sleep are 5 stages.

Distribution of Sleep Stages Female slides

In a typical night of sleep, a young Adult
• SWS occupies most of the total night sleep time ( 75-80%), it is interrupted by intervening REM
sleep periods, every 90 minutes . ( REM sleep occupies 20-25% of sleep time.)
• first enters into NREM sleep, passes through stages 1 , 2 , 3 & 4 SWS, then, 60-100 min from sleep
onset, goes into the first REM sleep episode.
• This cycle is repeated at intervals of about 90 min throughout the 8 hours of night sleep.
• There are 4-6 sleep cycles/night (& 4-6 REM periods per night)
• As the night goes on → there is progressive reduction in stages 3 & 4 sleep and a progressive ↑ in
REM sleep .
 EEG waves
● Stages of Sleep: recorded by EEG

Waves Frequency Type of activity Associated with/occurs

alpha -associated with a state of relaxation.

Smooth electrical activity
8-13hz -awake but non-attentive.
-large ,regular Alpha waves.

beta -associated with a state of arousal.

Irregular electrical activity
14-40hz -awake and attentive
-low amplitude, fast,irregular Beta waves.

-occurs intermittently during early stages

theta 4-7hz -
of slow wave sleep, and REM sleep.

Regular synchronous electrical -Occurs during the deepest stages of

delta less than 4hz activity (synchronous means all together so slow-wave sleep.
these waves will join together to form a big
wave)
 EEG waves
from Beta to Delta the Amplitude of the waves
increase
 REM Sleep (Paradoxical sleep) (Desynchronized sleep)
→ In a normal night of sleep, episodes(bouts) of REM sleep lasting for 5 to 30
minutes usually appear on the average after every 90 minutes (The first such period
occurring 80-100 minutes after the person falls asleep)
→REM sleep is not as restful as SWS .
→When the person is extremely sleepy, each episode of REM sleep is short(the
duration of each bout of REM is very short), and it may even be absent.
→Conversely, as the person becomes more rested through the night, the durations
of the REM episodes(bouts) increase.

● Possible cause of REM sleep: it's not understood why slow wave sleep is broken periodically by REM sleep.

Drugs that mimic the action of acetylcholine increase the occurrence of REM sleep. *REM sleep also called dreamful sleep.

It has been postulated that the large acetylcholine secreting neurons in the upper brain stem reticular
formation might through their extensive efferent fibers activate the brain, even though the signals are not
channeled appropriately in the brain to cause normal conscious that is characteristic of wakefulness.

This mechanism theoretically could cause the excess activity that occurs in certain brain
regions in REM sleep.
 Stages of slow-wave(non rapid eye movement) sleep Male slides

stage Description EEG Findings

● This is an initial stage between awakening and sleep
● It normally lasts from 1-7 min Alpha waves diminished and
1 ● The person feels relaxed with eyes closed Theta waves appear on EEG.
● If awakened, the person will frequently say that he has not been sleeping

● This is the first stage of true sleep

Shows sleep spindles
● The person only experiences only light sleep
(sudden,sharply pointed waves)
2 ● It’s a little harder to awake the person
12-14 hz (cycles/second).
● Fragment of a dream may be experienced
● Eyes may slowly roll from side to side

● This is the period of moderately deep sleep

● The person is very relaxed Shows mixture of sleep spindles
3 ● Body temperature begins to fall, B.P decreases and delta waves.
● Difficult to wake the person up
● This stage occurs about 20-25 min after falling asleep

4 ● Deep sleep starts person become fully relaxed, Respond slowly if awakened Dominant by delta waves.
Cont…
 Characteristics of REM sleep:
● There are rapid eye movements - REM sleep occupies 80% of total
sleep time in premature infants &
● Muscle tone throughout the body (except eye muscles) is 50% in full-term neonates.
- Thereafter, the proportion of REM
exceedingly depressed sleep falls rapidly and plateaus at
about 25% until it falls further in old
● Active form of sleep associated with dreaming age .
- Children have more total sleep time
● Difficult to arouse by sensory stimuli. & stage 4 sleep than adults.

● Heart rate and respiration become irregular which is

characteristic of a dream state.

● Brain is highly active in REM sleep and brain metabolism may be

increased by 20%.
● EEG.: Pattern shows brain wave of wakefulness, REM sleep is a type of
sleep in which the brain is quite active, but this brain :
-is not aware cut-off the external world.
-its activity is not channeled into purposeful external motor activity.
 Physiological Changes in Sleep
-Effects produced by awakening after
CVS: Pulse Rate, cardiac output, blood pressure & vasomotor tone 60-100 Minutes:
are decreased but the blood volume is increased because of reabsorption ( fluids
enter circulation)
1. Equilibrium disturbed.
2. Neuromuscular junction fatigue.
Respiration: Tidal volume & respiratory rate are decreased.
3. Threshold for pain is lowered.
BMR is decreased 10-15%.
4. Some cells shrink.
Urine volume: Decreased

Secretions: Salivary/lacrimal secretions are reduced, gastric/sweat

secretions are increased. Due to digestion

Reflexes: Superficial reflexes are unchanged except -Growth hormone,

plantex reflex, but Deep reflexes are reduced. melatonin, cortisol,
leptin, and ghrelin
levels are highly
Muscles: Relaxed correlated with
sleep and circadian
rhythmicity.
 Properties of Slow wave and REM Sleep
Properties Slow wave sleep REM sleep

Heart rate: → Slow decline Variable with high bursts

Respiration: → Slow decline Variable with high bursts

Autonomic
activities Thermoregulation: → Maintained Impaired

Brain temperature: → Decreased Increased

Cerebral blood flow: → Reduced High

Vivid dreams, well
Cognitive State — Vague thoughts
organized
Hormone Growth hormone:
High Low
secretion secretion →
 Cont…
Properties Slow wave sleep REM sleep

Progressively
Postural tension: → Eliminated
reduced
Skeletal
muscular Knee jerk reflex: → Normal Suppressed
system
Phasic twitches: → Reduced Increased

Infrequent, slow,
Eye movements: → Rapid, coordinated
uncoordinated
Neural firing Cerebral cortex Many cells reduced Increased firing rates,
rates (sustained) activity: → and more phasic tonic
Events related
Sensory-Evoked: → Large Reduced
potential
 Female slides
Mechanisms of Sleep
Although several theories of sleep have been proposed, most current evidence is in favor of
the following:

Serotonin, produced by Raphe Nuclei which is in the medulla oblongata,

1
induces SWS Sleep.

The mechanism that triggers REM sleep is located in the Pontine Reticular
2
formation & the Ponto-Geniculo-Occipital circuit is instrumental in
generation of REM sleep.

3 Melatonin (released from Pineal Gland) plays a role in day-night alteration

of sleep. (also given as supplements to help induce sleep)
 Female slides
Role of Serotonin & Melatonin in SWS
1 Raphe Nucleus (Serotonin)
-Stimulation of Raphe Nuclei (in the lower Pons & Medulla) Induces SW.
- Destruction of Raphe Nuclei renders 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 mid pons of an animal, leaves the animal in a state of
intense wakefulness for a period of days.
- The Transection cuts the nerves going from the inhibitory Serotonin-Secreting Raphe Nuclei to the
Bulboreticular Facilitatory area of the RAS, indication that the Serotonin-Secreting Raphe fibers
normally Inhibit the Bulboreticular Facilitatory area to produce sleep.

2 Melatonin
- Injection 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 & produce wakefulness. (that’s why we
sleep in the dark)
 Female slides
Physiological mechanisms of sleep & waking
1 Acetylcholine
- One of the most important neurotransmitters involved in arousal.
- Two groups of acetylcholinergic neurons are located in Pons & basal forebrain

2 Muramyl peptide
-induces sleep
Neural Activity of Neurotransmitter Systems During Sleep and Arousal

Activity During
Site of cell
Neurotransmitter
bodies Wakefulness SWS REM

Raphe
Serotonin High Low Very Low
Nuclei

Locus
Norepinephrine High Low Very Low
Coeruleus

Acetylcholine Brainstem High Low High

 The Reticular Activating System

● RAS: Is a diffuse network of nerve pathways in the brainstem connecting

the spinal cord, cerebrum, cerebellum and mediating overall level of
consciousness.

● Normal sleep is under control of the reticular activating system in the

upper brainstem and diencephalon
 Sleep disorders \ burden
-70 million people in the US suffer from sleep problems [50% have chronic sleep disorder]
Insomnia = 30 million (most common)
sleep apnea= 18 million
Narcolepsy= 250,000 Americans have
Motor Car Accidents= 100,000
traffic fatalities =1500 drowsy driving/annum (Per year)
-Approximately $16 billion annually the cost of healthcare in USA & result in $50 billion annually in lost productivity.

1 2 4
Disorder of slow wave sleep: Disorder of REM sleep:
1- Sleep talking / sleep walking 1- Nightmare: Frightening dream Drug dependency insomnia:
[common in children] (Awake from REM). An insomnia caused by the side
2- Night tremors: Are seen in III, IV 2- Sleep Paralysis: Subject awake but effect of ever increasing doses
stage of slow wave sleep unable to speak or move. of sleeping medications
[common in children]. 3- Sleeping Sickness.
3- Night terrors: Sudden arousal
from sleep and intense fear 3 5
accompanied by physiological Insomnia: Somnolence:
reactions (e.g., rapid heart rate, inability to sleep Extreme sleepiness
perspiration) that occur in SWS. Causes stress, affect social life
 Cont…
6 8 Narcolepsy:
A sleeping disorder characterized by periods of
Somnambulism: irresistible sleep, attacks of cataplexy, sleep paralysis, and
Walking during sleep hypnagogic hallucinations.
Excessive sleepiness may occur while talking, sitting,
decreased ability to regulate sleep.

7 Female slides
Sleep apnea: Symptoms of Narcolepsy
Cessation of breathing while
sleeping(failure to breathe 1- Sleep attack 2- Cataplexy 3- Sleep paralysis
when asleep) Especially in obese An irresistible urge Complete Paralysis
patients, causes heart and other to sleep during the paralysis that occurring just
serious diseases day, after which the occurs during before a person
person awakes walking. falls asleep.
feeling refreshed.
 TEST YOURSELF !
From team 439

1-State of unconsciousness from which a subject can be aroused by appropriate

sensory or other stimuli.

A) Coma B) Sleep C) Cataplexy D) Awake

2- Which of the following is true about REM sleep?

B) Increased phasic C) Occurrence is directly

D) Normal heart rate

Answers : B, B, A, C
A) High muscle tone twitches proportional with fatigue

3- which of the following is associated with a state of arousal?

A) Beta B) Alpha C) Theta D) Delta

4- Stimulation of the Supra-chiasmal nucleus of hypothalamus by light falling on

the retina inhibits which of the following?

A) Serotonin B)Acetylcholine C) Melatonin D) Muramyl peptide

 SAQ
1- what is the difference between sleep and coma ?
In slide 3

2- define NREM and REM sleep ?

In slide 9

3- mention some of the physiological changes in sleep?

In slide 16
 Team Leaders
Rafan Alhazzani
Sultan Albaqami
Aseel Alsaif
Aldanah Alghamdi Fahad Almughaiseeb
Huda bin Jadaan
Team Members
Bayan Alenazi Rahaf Alslimah Layla Alfrhan Hamad Alyahya Salmam Althunayan
Renad alshehri Jana Alshiban Farah Aldawsari Mishal aldakhail faisal alzuhairy
Razan Alsoteehi Manar Aljanubi Ziyad Alsalamah Mohammed Alarfaj
Layan Alruwaili
Omar Alamri Ryan alghizzi
Norah Alhazzani Lena Alrasheed Waad Alqahtani
Sultan almishrafi Mohammed Maashi
Haya Alzeer Layan Aldosary Salma Alkhlassi Mohammad Alzahrani Zeyad Alotaibi
Huda bin Jadaan Shahad Alzaid Shoug Alkhalifa Khalid Alanezi Nazmi Adel Alqutub
Haya Alajmi Norah Almania Sarah Alajajii Sami Mandoorah Faisal Alshowier
Reena alsadoni Lama Almutairi Sarah Alshahrani Abdullah Alzamil Ziad Alhabardi
AlJoharah AlWohaibi Raghad Alhamid Wafa Alakeel Mohammed Alqutub Osamah almubbadel
Reemaz Almahmoud
Special Thanks to Physiology Team441 Sarah Alshahrani
Team logo and design was done by Rafan Alhazzani
Thanks to ALEEN ALKULYAH for Helping with the design! med443physioteam@[Link]