Sleep & Wakefulness

Learning Objectives

• Define and describe endogenous rhythms.

• Explain the mechanisms that set and reset the biological
clock.
• List and characterize the stages of sleep.
• Describe the brain mechanisms of waking and sleeping.
• Examine the flip-flop model of sleeping and waking.
• List several sleep disorders with their causes.
• Evaluate possible explanations of the functions of sleep.
• Describe possible explanations of dreaming.
© Cengage Learning 2016
 Rhythms of Waking and Sleeping

• Early psychologists believed that cycles of

wakefulness and sleep were dependent
upon external stimuli
• Ex. Curt Richter in 1922 proposed that the
body generates its own cycles of activity
and inactivity

© Cengage Learning 2016

 Endogenous Circadian Rhythms

• All animals produce endogenous circadian

rhythms: internal mechanisms that operate
on an approximately 24 hour cycle
– Sleep cycle
– Frequency of eating and drinking
– Body temperature (36.7°C night, 37.2°C day)
– Secretion of hormones
– Urination
– Sensitivity to drugs
© Cengage Learning 2016
 Recording Biorhythms

Fig 13-2
Circannual
Circadian
Infradian
Ultradian
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 Daily Activity of a Squirrel Kept in Total
Darkness

Humans:
Slightly >24 hrs

© Cengage Learning 2016

 Fig 13-3

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 Daily Pattern of Positive Moods

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 Jet Lag

• Refers to the
disruption of the
circadian
rhythms due to
crossing time
zones
à mismatch of
the internal
circadian clock
and external
time
Fig 13-5
© Cengage Learning 2016
 Shift Work

• Working at night doesn’t reliably change the

circadian rhythm
• Adapting to graveyard shift is difficult and
stressful; increases susceptibility to disease
by altering immune system rhythms.
• People adjust best to night work if they sleep
in a very dark room during the day and work
under very bright lights at night
• Body temperature doesn’t adjust
© Cengage Learning 2016
 Mechanisms of the Biological Clock

• Mechanisms of the circadian rhythms

– The suprachiasmatic nucleus
– Genes that produce certain proteins
– Hormone levels

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 The Suprachiasmatic Nucleus (SCN)

• The main control center of the circadian

rhythms of sleep and temperature
– Located above the optic chiasm; part of the
hypothalamus

Fig 13-6

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 The Suprachiasmatic Nucleus (SCN) of
Rats and Humans

Daytime Night time

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 Suprachiasmatic Nucleus (SCN)

1. Activity in the
SCN correlates
with
circadian rhythms
ß

2. Isolated SCN in
cell culture
continues to show
a circadian activity
© Cengage Learning 2016
 Immortal Time (Ralph
& Lehman, 1991)

Lesion of à
ß the SCN:
Lack of
circadian
rhythm

© Cengage Learning 2016

Fig 13-7
 The SCN and the Circadian Rhythm

• SCN generates circadian rhythms in a

genetically controlled, unlearned manner
• Various cells communicate with each other to
sharpen the circadian rhythm

© Cengage Learning 2016

The SCN and the Retinohypothalamic Path
• SCN receives information about light via a
small branch of the optic nerve known as the
retinohypothalamic path
– Extends directly retina à SCN
– special population of RGCs: melanopsin
– The cells respond
directly to light
and do not require
any input from the
rods or cones
© Cengage Learning 2016
The SCN and the Retinohypothalamic Path

Fig 13-6
© Cengage Learning 2016
 The Biochemistry of the Circadian Rhythm

• In flies, two types of genes are responsible for

generating the circadian rhythm:
– Period (3): produce proteins called PER
– Cryptochrome (2) : produce proteins called CRY
• PER and CRY proteins increase the activity of
certain SCN neurons that
regulate sleep and waking
– Ex. Mutations in the PER
gene result in odd circadian rhythms or decreased
alertness if deprived of a good night’s sleep
© Cengage Learning 2016
 Circadian Timing System Organization

Fig 13-8

© Cengage Learning 2016

 Melatonin

• SCN regulates pineal gland (through the

ANS),
• pineal gland secretes melatonin, a hormone
that increases sleepiness
– Circulates during the dark
phase of the circadian cycle
– Promotes sleep,
rest-and-digest

© Cengage Learning 2016

 Glucocorticoids

• SCN regulates adrenal glands: located on

the kidneys
• adrenal glands secrete glucocorticoids
during light phase of circadian cycle:
promote arousal activities

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 Preoptic area and posterior
hypothalamus (Von Economo, 1917)
Study of patients who
died of flu epidemic.
• Damage in preoptic
area and adjacent
forebrain results in
wakefulness.
• Damage in posterior
hypothalamus and
adjacent midbrain
results in excessive
sleep.
© Cengage Learning 2016
Reticular Activating System (RAS) (Moruzzi
and Magoun, 1949)
Cerveau isolé “isolated forebrain”
preparation à permanent SWS

Encephale isolé
“isolated brain”
preparation à normal
sleep
The RAS controls both
wake AND REM sleep.

Stimulation of the
RAS > wakefulness
© Cengage Learning 2016
 NT systems controlling wakefulness

• Multiple systems
ACh – high frequency waves/wakefulness
5-HT – quiet waking state; reduced cortical
activation
NE – fight or flight / stressed waking response
Histamine – wakefulness (inhibit sleep)
DA – arousal; D2KOs sleep more
GABA & glutamate
• None are completely essential!!

© Cengage Learning 2016

 Histamine in the TMN

• Tuberomammillary nucleus (TMN) of the hypothalamus

-Most active during attentive wakefulness; silent during
sleep
• Widespread projections
• 3 Rs: H1, H2, H3
-H1 & H2 postsynaptic,
excitatory
-Antagonize H1Rs
à sedation
-H3 presynaptic,
inhibitory
© Cengage Learning 2016
 Ventrolateral Preoptic Nucleus of the
Hypothalamus (VLPO)
• GABAergic;
Active during sleep
• Reciprocal, inhibitory
projections with TMN
àFlip-flop model for
sleep/wake transitions

© Cengage Learning 2016

 Flip-flop model

• During wakefulness:
Histamine released
from TMN neurons
acts on inhibitory H3 receptors, reducing the
inhibition on itself (which is coming from
GABA inhibitory neurons from the VLPO,
and other structures too).
Histamine is also released on to excitatory H1
receptors on VLPO GABA interneurons,
increasing their inhibition of the VLPO.
© Cengage Learning 2016
 Flip-flop model

• During sleep:
TMN neurons are inactive, and VLPO is active
à GABAergic inhibition of TMN

© Cengage Learning 2016

 Adenosine

• Brain ATP dephosphorylated to adenosine

• Adenosine activates G protein coupled

receptors on neurons: A1, A2A, A2B, A3
• A1 & A2A receptors very sensitive to
adenosine; activated at the normal levels of
circulating adenosine à leads to reduction of
neuron excitability and NT release.

© Cengage Learning 2016

 Adenosine

• Accumulation of adenosine during periods of

wakefulness depresses the activity of neurons
in the TMN, thus precipitating sleepiness.
• This explains the
stimulant action
of caffeine, since
caffeine blocks
adenosine Rs
à adenosine can’t
have its effects!
© Cengage Learning 2016
 Brain Mechanisms of Wakefulness and
Arousal – Locus Coeruleus
• The locus coeruleus is a small structure in the
pons whose axons release norepinephrine to
arouse various areas of the cortex and
increase wakefulness
– Usually dormant while
asleep

© Cengage Learning 2016

 Brain Mechanisms of Wakefulness and
Arousal – Basal Forebrain
• Acetylcholine neurons in the basal forebrain
stimulate neurons responsible for wakefulness and
arousal
• Some cells of the basal
forebrain also release
inhibitory GABA
– Inhibition provided by GABA
is essential for sleep
• Inhibits spontaneously active
neurons
• Flip-flop model
© Cengage Learning 2016
 Sleep as a Local Phenomenon

• Sleep can be localized within the brain

– Sleepwalkers: awake in one part of the brain and
asleep in others
– Lucid dreaming: dreaming but aware of being
asleep and dreaming
[Link]

– Pons paralysis: the pons remaining in REM while

other brain areas wake up; causes the inability to
move
© Cengage Learning 2016
 Brain Structures for Arousal and Sleep

[Link]
?v=P7BR5rwUbak

© Cengage Learning 2016

 The Electroencephalogram (EEG)

• Measures the activity of cortical neurons

• The electrical signal results from the summation of
the activity of thousands of neurons.
• Synchronized neurons
– High amplitude brain waves

• Desynchronized neurons
– Low amplitude brain waves
© Cengage Learning 2016
 What is Sleep?

Before 1929: sleep is a unique passive state of

immobility caused by the a general reduction or
cessation of brain activity leading to lack of
perception of the external world and lack of
consciousness.
1929-1953: Sleep is a unique active state of immobility

>1953: Sleep is a specialized state evolved to serve

particular functions, composed of different states
AND is associated with localized high brain activities
© Cengage Learning 2016
 Sleep

• Sleep is a state of consciousness that the

brain actively produces
– Characterized by a moderate decrease in
brain activity and decreased response to
stimuli
• Two general categories: Non-REM (quiet,
4 stages) & REM (active) sleep

© Cengage Learning 2016

 Sleep Stages

Alpha
Burst
8-12 Hz
Theta
5-8 Hz

Delta
© Cengage Learning 2016 1-4 Hz
 Stage 1 Sleep

• Alpha waves are present when one begins a

state of relaxation (a)
• Stage 1 sleep (b) is when sleep has just begun
– The EEG is dominated
by irregular, jagged,
and low voltage waves
– Brain activity begins to
decline

© Cengage Learning 2016

 Stage 2 Sleep

• Stage 2 sleep (c) is characterized by the

presence of:
– Sleep spindles: 12- to 14-Hz waves during a burst
that lasts at least half
a second
– K-complex: a sharp
wave associated with
temporary inhibition of
neuronal firing

© Cengage Learning 2016

 Slow Wave Sleep – Stage 3 and Stage 4

• Stage 3 (d) and stage 4 (e) often are

considered together to constitute deep, slow
wave sleep (SWS). SWS is characterized by:
– EEG recording of slow,
large amplitude wave
– Slowing of heart rate,
breathing rate, and
brain activity
– Highly synchronized
neuronal activity
© Cengage Learning 2016
 REM Sleep

• AKA paradoxical sleep because it’s deep

sleep in some ways, but light sleep in
other ways.
• EEG waves are irregular, low-voltage, and
fast, plus breathing and heart rates similar
to stage 1 sleep.
• Postural muscles of the body are atonic

© Cengage Learning 2016

 NREM and REM Cycles

• When people fall asleep, they progress

through stages 1, 2, 3, and 4 in sequential
order
– After about an hour, the person begins to cycle
back through the stages from stage 4 to stages 3
and 2 and then REM
– The sequence repeats
with each cycle lasting
~90 minutes

© Cengage Learning 2016

 A Typical Night’s Sleep

Fig 13-12
© Cengage Learning 2016
 Brain Function in REM Sleep

• During REM sleep:

– Activity increases in pons, limbic system,
parietal & temporal cortex
– Activity decreases in V1, M1, dlPFC

• REM sleep associated with distinctive pattern of

high-amplitude electrical potentials = PGO waves:
Waves of neural activity detected first in the pons,
soon afterward in the lateral geniculate nucleus, and
then occipital cortex
© Cengage Learning 2016
 Brain Function in REM Sleep (cont’d.)
• Cells in the pons send messages to the spinal cord,
which inhibits motor neurons that control the body’s
large muscles
– Prevents motor movement
during REM sleep
• REM is also regulated by
serotonin and acetylcholine
(onset & continuation)
– AChR agonists quickly move people to REM
– Serotonin interrupts REM
– NE from LC blocks REM sleep
© Cengage Learning 2016
 Narcolepsy

• A sleep disorder characterized by frequent,

unexpected periods of sleepiness (during the
day). Symptoms include:
– Gradual or sudden attack of sleepiness
– Occasional cataplexy
– Sleep paralysis
– Hypnagogic hallucinations: dreamlike experiences

© Cengage Learning 2016

 Narcolepsy

• Caused by lack of hypothalamic cells that

produce and release orexin
• Primary treatment
is with stimulant
drugs
(Ritalin/
methylphenidate)
à enhance
dopamine and
norepinephrine
© Cengage Learning 2016
 Periodic Limb Movement Disorder

• The repeated involuntary movement of the

legs, and sometimes the arms, while
sleeping
– Legs kick once every 20 to 30 seconds for
periods of minutes to hours
– Usually occurs during NREM sleep
– Can cause insomnia
– May be treated with tranquilizers

© Cengage Learning 2016

 REM Behaviour Disorder

• Associated with vigorous movement

during REM sleep
– Usually associated with acting out dreams
• Research suggest that inadequate GABA
and other neurotransmitters may be
responsible
– Pons doesn’t inhibit spinal motor neurons

© Cengage Learning 2016

 Why Sleep? Why REM? Why Dream?

• We’ve evolved inhibitory processes in our brains

that force us to become less aroused and less
alert, thus to sleep
• Some of the many functions of sleep include:
– Resting muscles
– Decreasing metabolism
– Performing cellular maintenance in neurons
– Reorganizing synapses
– Strengthening memories
© Cengage Learning 2016
 How much sleep do you actually need?

• [Link]
xiQlzI

• Sleep as/is a restorative process!

© Cengage Learning 2016

 Genes and sleep

• [Link]
medicine/study-reveals-gene-mutation-
makes-you-need-less-sleep/
• Twin study
• One variant of a gene, called Y362H, in
one twin in a fraternal pair conferred
reduced sleep duration. Even after sleep
deprivation, he needed less recovery
sleep and showed fewer performance
lapses than his twin.
© Cengage Learning 2016
 Sleep & Memory
• Sleep enhances learning & strengthens memory
– Performance on a newly learned task is often
better the next day if adequate sleep is achieved
– Increased brain activity occurs in the area of the
brain activated by a newly learned task
Fig 13-20

© Cengage Learning 2016

 Sleep & Memory (cont’d.)

• Patterns of activity in the hippocampus during learning

were similar to those shown during sleep
– Suggests that the brain rapidly replays its daily
experiences during sleep

Fig 13-19

© Cengage Learning 2016

 Sleep improves memory performance

• Sleep improves
performance
• Improvement is
correlated with NREM
and REM

© Cengage Learning 2016 Allyn & Bacon, 2009

Replay of neuronal memories during NREM
sleep

© Cengage Learning 2016

 Amounts of REM Sleep

• Humans spend one-third of their life asleep;

about one-fifth is spent in REM
• Species vary in amount of sleep time spent in
REM
– Most common in birds and mammals
– Percentage of REM sleep is positively correlated
with the total amount of sleep in most animals
– Among humans, those who get the most sleep
have the highest percentage of REM

© Cengage Learning 2016

 Amounts of REM Sleep

• Humans spend one-third of their life asleep;

about one-fifth is spent in REM
– Depriving NREM
vs
– Depriving REM

à REM sleep implicated as a useful tool for

memory storage / consolidation.

© Cengage Learning 2016

 Sleeping & Waking Over the Lifespan

Fig 13-13

© Cengage Learning 2016

 Biological Perspectives on Dreaming

• Biological research on dreaming is

complicated by the fact that subjects
cannot often accurately remember what
they were dreaming or had dreamed
• Two of the biological theories of dreaming
include:
– The activation-synthesis hypothesis
– The clinico-anatomical hypothesis

© Cengage Learning 2016

 The Activation-Synthesis Hypothesis

• Suggests that dreams begin with

spontaneous activity in the pons, which
activates many parts of the cortex
– The cortex synthesizes a story from the
pattern of activation
– Normal sensory information is sometimes
integrated, but usually is not
– When dreaming, you really can’t move; this is
also a common dream

© Cengage Learning 2016

 The Clinico-Anatomical Hypothesis

• Places less emphasis on the pons, PGO

waves, or even REM sleep:
– Suggests that dreams are similar to thinking,
just under unusual circumstances
• Similar to the activation-synthesis
hypothesis, in that dreams begin with
arousing stimuli that are generated within
the brain
– Stimulation is combined with recent memories
and information from the senses
© Cengage Learning 2016
The Clinico-Anatomical Hypothesis (cont’d.)

• Because the brain is getting little

information from the sense organs, images
are generated without constraints or
interference
• Arousal cannot lead to action, as the
primary motor cortex and the motor
neurons of the spinal cord are suppressed
• Activity in the prefrontal cortex is
suppressed, which impairs working
memory during dreaming
© Cengage Learning 2016
 The Clinico-Anatomical Hypothesis –
Conditions
• Activity is high:
– In the inferior part of the parietal cortex, an area
important for visual-spatial perception
• Patients with damage report problems in binding body
sensations with vision, and have no dreams
– In areas outside of V1, accounting for the visual
imagery of dreams
– In the hypothalamus and amygdala, which
accounts for the emotional and motivational
content of dreams
© Cengage Learning 2016
 A more psychological approach to sleep…

• Mood Regulatory Function of dreams

– (aka Coping Dream Hypothesis – next slide)
• Problem Solving Hypothesis of dreaming
(Diedre Barrett)

• Cognitive Hypothesis of dreaming

• Freud’s Latent Content

© Cengage Learning 2016

 Dreams as Mood Regulation (Coping)

• Dreaming modulates disturbances in emotion

• negative mood is down-regulated overnight.
• experience gets reactivated in sleep and carried
forward into REM; it is matched by similarity in
feeling to earlier memories; activations get displayed
as a sequence of compound images
• This modifies the network of emotional self-defining
memories; updates our self-image
• Dreaming diffuses the emotional charge of the event;
wake up recharged/refreshed
© Cengage Learning 2016