Sleep

Ty Lees
School of Life Sciences

Ty.Lees@uts.edu.au
Copyright: Sara Lal, Bear et al, Neuroscience: Exploring the Brain, Video tutorial & UTS,
Kolb & Whishaw (2004), An Introduction to Brain and Behaviour, 2nd ed., Worth
Publishers, USA. Purves et al., (2008), Neuroscience, 4th ed., Sinauer Associates Inc, USA.
Objectives
Bear et al., Chapter 19

After this lecture you should be able to:

Discuss functional brain states and the stages of sleep
Compare non-REM and REM sleep in terms of timing,
progression and EEG correlates
Discuss the function and role of the reticular activating system
and suprachiasmatic nucleus
Understand the impact of the adenosine in sleep
Explain circadian rhythms and their role
Discuss sleep talking/sleep walking and narcolepsy in
relationship to the concepts of sleep
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Sleep
Universal among higher vertebrates
Sleep deprivation, devastating
Functionally, not physically
One-third of lives in sleep state

Defined: Sleep is a readily reversible state of

reduced responsiveness to, and interaction with,
the environment.

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Functional Brain States

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Sleep Monitors

Sleep measuring
devices monitor:
EEG, EMG and EOG,
respiration,
temperature, etc.

Sleep researchers call

these recordings: a
polysomnogram

Adapted from: Kolb & Whishaw (2004)

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Stages of Sleep
Classic Definition (Rechtschaffen and Kales (R & K), 1968)
Wakefulness
Non-REM sleep
Stage 1 (Drowsiness/light sleep)
Stage 2 (Light sleep)
Stage 3 (Slow wave sleep/deep sleep)
Stage 4 (Slow wave sleep/very deep sleep)
REM (Rapid eye movement)

Updated Definition (combined Stages 3 & 4 American Academy of Sleep Medicine (AASM) , 2007)
Wake
Non-REM
Stage N1 (Equivalent to R & K Stage 1)
Stage N2 (Equivalent to R & K Stage 2)
Stage N3 (R & K Stages 3 & 4 combined, since no physiological or clinical basis for difference)
REM (Stage R)

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Sleep stage progression

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Non-REM Sleep
N1 or Stage 1
Drowsy, transitional sleep, EEG alpha of relaxed, increasing theta
Waking less regular, slow rolling eye movements

N2 or Stage 2
Slightly deeper sleep, sleep spindles present (generated by thalamic
pacemaker). High amplitude sharp wave called K complex observed
Little eye movement

N3 or Stage 3 & 4
Stage 3
EEG large amplitude slow delta rhythms
No eye and body movement
Stage 4
Deepest sleep, large EEG rhythms of 2 Hz or less

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Stage R/REM Sleep

Fast EEG beta waves, frequent eye movement

As the night progresses

Reduction in non-REM sleep
Increased REM periods

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Physiological Changes during sleep

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The reason for sleep
Recovery time for brain?

Restoration?
Sleep to rest and recover, and prepare to be awake
again

Adaptation?
Sleep to keep out of trouble, hide from predators

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Neural Mechanisms of Sleep
Critical neurons Diffuse modulatory neurotransmitter
systems

Noradrenergic and serotoninergic neurons: Fire during and

enhance waking state

Cholinergic neurons: enhance REM events; active during waking

Diffuse modulatory system control rhythmic behaviors of

thalamus controls cortical EEG sensory input flow to
cortex blocked by slowed thalamic rhythms

Activity in descending branches of diffuse modulatory systems

(e.g., inhibitory neurons)

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Wakefulness & the reticular system
Several sets of neurones
increase activity in
anticipation of awakening
and during arousal.

They include locus coerulus

cells which contain
noradrenaline, serotonin
containing cells and
acetylcholine containing
cells and neurones of the
midbrain that use histamine
as neurotransmitter.
Adapted from: Kolb & Whishaw (2004)
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Falling Asleep & NREM state
Sleep: Progression of changes ending in non-REM
state

Non-REM sleep: Decrease in firing rates of most

brain stem modulatory neurons using NE, 5-HT, ACh

Stages of non-REM sleep:

EEG sleep spindles
Spindles disappear
Replaced by slow, delta rhythms (less than 4 Hz)

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REM Sleep
Neurones of the motor cortex
fire rapidly during REM.
Dreams of REM sleep require the
cerebral cortex.
Extrastriate cortex and portions
of the limbic system (emotional
component of dreams) are
active during REM.
Control of REM sleep, derives
from diffuse modulatory systems
in the brain stem, particularly
pons.
Some evidence suggests that
cholinergic neurons induce REM
sleep.
Adapted from: Kolb & Whishaw (2004)
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REM Sleep

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Adenosine & Sleep
It has an inhibitory effect on the diffuse modulatory systems for
ACh, NAd, and 5-HT that are active in the awake brain.

Neural activity in brain increases adenosine, as it increases

during waking hours, there is more inhibition of modulatory
system neurons associated with wakefulness.

Increased suppression of the wakeful modulatory systems

increases the likelihood that the brain will fall into the slow-
wave activity characteristic of sleep.

After sleep begins adenosine levels slowly fall, and activity in

the modulatory systems increases until we wake.

Adenosine- cue that the brain needs time for restoration.

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Circadian Rhythms
Circadian rhythms
Circa= approximately
Dies = a day
Daily cycles of light and
dark
Schedules of circadian
rhythms vary among
species
Physiological and
biochemical processes in
body: rise and fall with
daily rhythms
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Suprachiasmatic Nuclei (SCN)
SCN in the hypothalamus is the
biological clock of mammals
Zeitgebers (German for time-
givers):Zeitgebers: a rhythmically occurring natural phenomenon which acts
as a cue in the regulation of the body's circadian rhythms.
Environmental time cues
For mammals primarily light/dark
cycle
Photosensitive mechanism to reset
the brain clock via the
retinohypothalamic tract
Axons from retinal ganglion cells
synapse with dendrites of SCN
neurones
Input from retina is necessary to
entrain sleeping and waking cycles
to night and day Adapted from: Purves et al. (2008)
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SCN Mechanisms
The Suprachiasmatic Nucleus: A Brain Clock
Intact SCN produces rhythmic message:
SCN cell firing rate varies with circadian
rhythm
Each SCN cell is a small clock

A New Type of Photoreceptor

Berson and colleagues: Discovered
specialized type of ganglion cell in retina
Photoreceptor, but not rod or cone cell
Contains melanopsin, slowly excited by
light
Synapses directly onto SCN neurons
SCN output axons: Parts of the
hypothalamus, midbrain, diencephalons,
use GABA as primary neurotransmitter,
lesions disrupt circadian rhythms
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SCN & Circadian Rhythms

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Sleep disturbances
Non-REM sleep can have walking, talking, screaming
REM associated with total body paralysis; impossible to walk &
talk in REM

Sleepwalking or somnambulism:
Peaks at 11yrs
40% sleep walk as children, few as adults
During first stage 4 period of non-REM
Eyes open, walk inside or outside & have awareness to avoid objects
Difficult to awake sleep walkers since they are in deep slow wave sleep,
guide them back to safety
No memory of the incident the next morning

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Sleep disturbances
Sleep talking or somniloquy done by most, now and then
Nonsensical and garbled talking

Sleep terrors:
Common in children aged 5-7 years, with screams in the middle of the
night
Begin in stage 3 or 4 of non-REM sleep
Greatly increased heart rate and blood pressure
Distress, and children generally inconsolable, approximately 10 min later
fall asleep again, quietly
No recollection next morning
Disappears with age- not a symptom of psychiatric disorder
Sleep terrors are different from nightmares,
Latter vivid, complex dreams, outwardly quiet, that occur
during REM sleep

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Narcolepsy
Bizarre disturbance of sleeping and waking, includes: excessive
daytime sleepiness and sleep attacks

Cataplexy (sudden muscular paralysis while conscious)

Middle of the day, sufferers suddenly collapse into a state similar to REM sleep
Can be brought on by strong emotion, such as laughter or tears or surprise-
usually lasts less than a minute

Sleep paralysis (also loss of muscle control)

Occurs during transition between sleep and waking
Sometimes occur in the absence of narcolepsy, and person may be unable to
move or speak for several minutes

Hypnagogic hallucinations
Are graphic dreams, often frightening, and accompany sleep onset and may
follow sleep paralysis

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EEG: Narcolepsy vs normal
Narcolepsy
Goes directly from waking into REM phase, i.e., abnormal intrusion of
REM sleep into waking
Normal sleep
Always enter a long period of non-REM sleep first

Genetic component: high % of people with narcolepsy have particular

form of human leukocyte antigen (HLA) gene.
Cholinergic and catecholaminergic systems implicated
Pharmacologically increasing dopamine output from the ventral
tegmental area induces cataplexy in narcoleptic animals, as the output
from this nucleus is associated with emotion and reward, it may explain
the fact that emotion trigger cataplexy
No known cure for narcolepsy- treatment tries to relieve symptoms
Frequent naps, amphetamines, new drug called modafinil may help
reduce daytime sleepiness
Tricyclic antidepressants (suppresses REM) may reduce cataplexy
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