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Chapter 9
Copyright © Allyn & Bacon 2010
Lecture Preview
 A Physiological and Behavioral Description of Sleep
 Disorders of Sleep
 Insomnia
 Narcolepsy
 REM sleep behavior disorder
 Problems associated with SWS
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and Waking
 Biological Clocks
Lecture Preview
 A Physiological and Behavioral Description of Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Functions of SWS
 Functions of REM sleep
 Sleep and Learning
 Physiological Mechanisms of Sleep and Waking
 Biological Clocks
Functions of Sleep
 Sleep is universal among vertebrates
 Only warm-blooded vertebrates (mammals & birds)
exhibit REM
 Sleep appears to be essential for life
 Bottlenose dolphin
 Extremely motivating to sleep – suggests a necessity of
life
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Functions of SWS
 Sleep deprivation studies with humans
 Sleep does not appear to play a role in rest and
recuperation of body


Sleep deprivation does not interfere with people’s ability to
perform physical exercise
No evidence of physiological stress response to sleep
deprivation
 Deficits in cognitive abilities

Perceptual distortions, hallucinations, trouble concentrating
on mental tasks
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Functions of SWS
 Sleep deprivation studies with humans
 Once sleep deprived Ss are allowed to sleep, they never
regain the total sleep they lost

7% of stages 1 and 2, 68% of SWS, 53% of REM
 Appears that the brain rests during sleep
 SWS may destroy free radicals
 Fatal familial insomnia (related to mad cow disease)
 Deficits in attention and memory
 Dreamlike, confused state, loss of control of ANS,
insomnia, fatal
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Functions of SWS
 Studies with lab animals
 Sleep deprivation is fatal

Not sure why
 Effects of exercise on SWS
 Not related
 Effects of brain activity on SWS
 Increased SWS following cognitive task
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Functions of REM Sleep
 Intense physiological activity
 Eyes dart, heart rate accelerates/decelerates, breathing becomes irregular,
brain becomes more active
 As REM deprivation persists, pressure to enter REM builds up
 After several days of REM deprivation - rebound phenomenon
 When allowed to sleep, greater than normal percentage of time in REM
sleep
 Important in neural development
 Premature infants, REM begins ~ 30 weeks, peaks ~ 40 weeks
 ~ 70% of newborn sleep is REM, at 6 months – 30%, late adulthood – 15%
 Why is it still present post-development?
 Learning and memory
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Sleep and Learning
 Sleep aids in the consolidation of long-term
memories.
 REM sleep facilitates the consolidation of nondeclarative
memory.
 Slow-wave sleep facilitates the consolidation of
declarative memory.
Two Categories of Memory
 Declarative/Explicit - conscious
recollection of facts & events (semantic &
episodic memories)
 Nondeclarative/Implicit - experience
can alter behavior without us being
consciously aware of exactly what we
have learned
Categories of Memory
Memory
Declarative
or Explicit
Facts
Events
Nondeclarative
or Implicit
Skills
Habits
Priming
Classical Nonassociative
Conditioning
Learning
Sleep and Learning
 REM sleep facilitates the consolidation of
nondeclarative memory.
 Ss learn a nondeclarative visual discrimination task
at 9am
 Test – 7pm
 Some Ss took a 90 min nap – EEG
 Ss with no nap < Ss with SWS < Ss with REM
Sleep and Learning
 Peigneux et al, 2004
 Ss (humans) learned their way around a computerized
virtual-reality town
 Hippocampus-dependent
 fMRI – same regions of the hippocampus were activated
during route learning and during SWS the following
night
 Although people who are awakened during SWS seldom
report dreaming, sleeping brain rehearses information
that was acquired during the previous day
 Consistent with animal data
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Lecture Preview
 A Physiological and Behavioral Description of Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and Waking
 Chemical control of sleep
 Neural control of arousal
 Neural control of SWS
 Neural control of REM
 Biological Clocks
Chemical Control of Sleep
Sleep is regulated – by what?
 If deprived of SWS or REM, animal will make up for at
least part of the missed sleep
 Amount of SWS during daytime nap is deducted from
the amount of SWS that night
Adenosine (nucleoside) – primary role in the control of
sleep
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Chemical Control of Sleep
Adenosine
 Astrocytes maintain a small stock of glycogen
 Increased brain activity – glycogen is converted to fuel
for neurons (glucose)
 Prolonged wakefulness causes a decrease in glycogen in
brain
 Fall in glycogen causes an increase in extracellular
adenosine
 Inhibitory effect on neural activity
 Accumulation of adenosine – sleep promoting substance
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Chemical Control of Sleep
Adenosine
 During SWS, neurons rest, astrocytes renew stock of
glycogen
 If wakefulness is prolonged, more adenosine
accumulates, inhibits neural activity
 Produces cognitive and emotional effects of sleep
deprivation
 Caffeine blocks adenosine receptors
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Adenosine
 Genetic factors affect the typical duration a person
spends in SWS
 Variability in the gene that encodes for adenosine
deaminase (enzyme that aids in breakdown on
adenosine)
 People with G/A allele for this gene (breaks down
adenosine more slowly), spent ~ 30 more min in SWS
than people with G/G allele (more common0
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Lecture Preview
 A Physiological and Behavioral Description of Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and Waking
 Chemical control of sleep
 Neural control of arousal
 Neural control of SWS
 Neural control of REM
 Biological Clocks
Neural Arousal
 Alertness can vary, regardless of sleepiness
 5 NTs play a role in alertness and wakefulness:
 ACh
 NE
 5-HT
 Histamine
 Orexin
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Acetylcholine (ACh)
3 groups of ACh neurons
 Pons
Activation & cortical desynchrony
 Basal forebrain
 Medial septum
 Controls activity of
hippocampus
(basal
forebrain)
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Neural Control of Arousal
 ACh
 ACh agonists increase EEG signs of cortical arousal
 ACh antagonists decrease them
 High levels of ACh in hippocampus and neocortex
during REM and waking, low during SWS
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Neural Control of Arousal
NE
 Locus coeruleus – located in dorsal pons
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NE
 Most neuron that release NE
do not do so at terminal
buttons but through axonal
varicosities
 Axonal Varicosities – beadlike
swellings of the axonal
branches, contains synaptic
vesicles and releases a
neurotransmitter or
neuromodulator.
Neural Control of Arousal
NE
 Activity of NE neurons was closely related to
behavioral arousal
 Firing rate was high during wakefulness, low during
SWS, almost zero during REM
 Within a few seconds of awakening, firing rate
increased dramatically
 Increase vigilance – ability to pay attention to stimuli
in the environment
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NE
 Carter et al., (2010) used viral vector to insert genes for
ChR2 and NpHR (photosensitive proteins), into NE
cells of LC
 Exposure of ChR2 to blue light activates the neurons
 Exposure of NpHR to yellow light inhibits the neurons
 Stimulation of the neurons caused immediate waking,
inhibition decreased wakefulness and increased SWS
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Neural Control of Arousal
5-HT
 Stimulation of RN causes locomotion and cortical arousal
 PCPA (antagonist) – reduces cortical arousal
 Neurons most active
during waking
 Firing rate decline
during SWS
 Zero during REM
 Facilitate continuous,
automatic movements
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Neural Control of Arousal
Histamine
 Cell bodies located in the
tuberomammillary nucleus (TMN) of
the hypothalamus
 Connections to cortex – increase cortical
activation and arousal
 Activity of histamine neurons is high
during waking, low during SWS and
REM
 Histamine antagonists decrease waking,
increase sleep
 Antihistamines
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Neural Control of Arousal
 Orexin (hypocretin)
 Cells bodies located in lateral hypothalamus
 ~7000 orexin neurons – project to almost every part of
brain
 Excitatory
 Orexin neurons fired at a high rate during alert or
active waking and at a low rate during quiet waking,
SWS and REM
Copyright © Allyn & Bacon 2010
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Lecture Preview
 A Physiological and Behavioral Description of Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and Waking
 Chemical control of sleep
 Neural control of arousal
 Neural control of SWS
 Neural control of REM
 Biological Clocks
Neural Control of SWS
What controls activity of arousal neurons?
 Preoptic area (POA) – control of sleep
 Contains neurons whose axons inhibit arousal neurons
 Destruction of POA produced total insomnia in rats
 Animals fell into a comma and died (3 days)
 Stimulation produced signs of drowsiness, sleep
 Ventrolateral POA (vlPOA)
 Damage suppresses sleep, increased Fos during sleep
 Release GABA – send axons to orexin, ACh, NE, 5-HT,
histamine neurons
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Neural Control of SWS
 POA neurons receive inhibitory input histamine, 5-
HT, NE neurons
 Mutual inhibition may control sleep/wake periods
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Figure 9.14
Copyright © Allyn & Bacon 2010
Neural Control of SWS
 Flip-flop advantage – quick switches from one state to
the other
 Flip-flop disadvantage – they can be unstable
 Narcolepsy – great difficulty remaining awake, trouble
remaining asleep
 Orexin neurons help stabilize the sleep/wake flip-flop
through excitatory connections to the wakefulness
neurons
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Figure 9.15 Role of Orexinergic Neurons in Sleep
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Neural Control of SWS
 Target mutation of orexin neurons
 Normal amounts of sleep and waking

Orexin not directly involved in regulating total amount of time
spent in sleep/wake
 Animals bouts of wakefulness and SWS were very brief

narcoplepsy
 Biological clock controls rhythms of sleep/wake
 Also receive signals from neurons that monitor nutritional
state
 Hunger-related signals activate orexin neurons, satiety
inhibits them
 Orexin neurons maintain arousal during the times when an
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animal should search for food
LECTURE PREVIEW
 A Physiological and Behavioral Description of
Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and
Waking




Chemical control of sleep
Neural control of arousal
Neural control of SWS
Neural control of REM
 Biological Clocks
NEURAL CONTROL OF REM SLEEP
 REM sleep is controlled by a flip/flop
•
Controls cycles of REM & SWS
 Similar to the one that controls sleep/wake
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Neural Control of REM Sleep

Sublaterodorsal Nucleus (SLD) – region of
the dorsal pons containing REM-ON cells.

Ventrolateral Periaqueductal Gray Matter
(vlPAG) – region of the
dorsal midbrain containing
REM-OFF cells.
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NEURAL CONTROL OF REM SLEEP
 REM-On and REM-OFF regions are
connected by inhibitory GABAergic neurons
•
•
•
•
Stimulation of REM-ON region – REM
Inhibition of REM-ON region – disrupts REM
Stimulation of REM-OFF region – suppresses REM
Inhibition of REM-OFF region – increase REM
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NEURAL CONTROL OF REM SLEEP
 During waking, REM-OFF region receives
excitatory input from orexinergic (ORXN) neurons
of LH
•
NE & 5-HT
 When sleep/wake switches to sleep, SWS begins
•
•
Activity of excitatory ORXN, NE, & 5-HT inputs to REM-OFF
region decrease
REM begins
 Internal clock – pons?
•
Controls alternating periods of REM and SWS
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Figure 9.20 REM Sleep
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NEURAL CONTROL OF REM SLEEP
 Degeneration of orexin neurons causes narcolepsy
 Daytime sleepiness and fragmented sleep occur
without orexin, sleep/wake flip-flop becomes
unstable
 Orexin normally keeps REM-OFF
 Without orexin, emotional episodes (activate
amygdala) turn REM-ON (cataplexy)
•
When people with cateplexy watched humorous photos,
hypothalamus was activated less, amygdala was activated
more (than controls)
 Loss of orexin neurons removed an inhibitory
influence of hypothalamus on amygdala
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Figure 9.20 REM Sleep
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NEURAL CONTROL OF REM SLEEP
 Neurons responsible for muscular paralysis are
located just ventral to REM-ON region (SLD)
 Axons project to spinal cord, excite inhibitory
interneurons which synapse onto motor neurons
 When REM flip-flop is on – motor neurons in spinal
cord become inhibited (don’t respond to motor
cortex)
 Damage to REM-ON region removes inhibition –
acts out dreams
 See figure 9.23
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NEURAL CONTROL OF REM SLEEP
Neurons in SLD (REM-ON) region also send axons
to:
 Thalamus
•
Control of cortical arousal
 Glutamatergic neurons in medial pons RF – ACh
neurons of basal forebrain
•
Arousal and cortical desynchrony
 ACh neurons to tectum
•
Rapid eye movements
Copyright © Allyn & Bacon 2010
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LECTURE PREVIEW
 A Physiological and Behavioral Description of
Sleep
 Disorders of Sleep
 Why Do We Sleep?
 Physiological Mechanisms of Sleep and Waking
 Biological Clocks




Circadian rhythms and zeitebers
The suprachiasmatic nucleus (SCN)
Control of Seasonal Rhythms: the pineal gland and
melatonin
Changes in circadian rhythms: shift work and jet lag
Biological Clocks
 Circadian Rhythms and Zeitgebers
•
•
Circadian Rhythms – daily rhythmical change in behavior or
physiological process.
Zeitgebers – stimulus that resets the biological clock
responsible for circadian rhythms.
• Maintains 24 hour clock
• If our biological clock runs free (in the case of constant
illumination), cycle ~25 hours
BIOLOGICAL CLOCKS
 The Suprachiasmatic Nucleus
(SCN)
•
•
•
A hypothalamic nucleus containing
the biological clock for many of the
body’s circadian rhythms.
Lesions disrupt circadian rhythms of
wheel running, drinking, and
hormonal secretions
Provides primary control over the
timing of sleep cycles
• Lesions disrupt sleep pattern –
sleep occurs in random bouts
dispersed throughout day and
night
•
Same amount of sleep
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BIOLOGICAL CLOCKS
 SCN
•
•
•
Light is the primary zeitgeber for most activity cycles
Direct projection from retina to SCN
• Retinohypothalamic pathway
Special photoreceptor that provides info about the ambient
level of light that synchronizes circadian rhythms
• Photochemical – melanopsin (ganglion cells, not
rods/cones)
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BIOLOGICAL CLOCKS
 How does SCN control sleep/wake cycle?
 SCN project to subparaventricular zone (SPZ) –
dorsal to SCN
SPZ
DMH
vlPOA & Orexin in LH
 Projections to vlPOA are inhibitory – inhibit sleep
 Projections to orexin neurons in LH are excitatory
– promote wakefulness
 Activity of connections vary across day/night cycle
 Figure 9.26
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Biological Clocks
 Control of Seasonal Rhythms: The Pineal Gland
and Melatonin

Pineal Gland – gland attached to the dorsal tectum;
produces melatonin and plays a role in circadian and
seasonal rhythms.
 SCN make indirect connections with PVN, spinal
cord, pineal gland

In response to input from SCN, pineal gland secretes
melatonin during the night
 Melatonin acts back on various brain areas (including
SCN), and controls hormones, physiological process,
behaviors that show seasonal variations
Biological Clocks
 Changes in Circadian Rhythms:
•
•
•
•
•
Abrupt changes in daily rhythms desynchronizes internal
circadian rhythms controlled by the SCN.
• E.g., Shift Work and Jet Lag
This desynchronization produces sleep disturbances and
mood changes, disrupts functioning during normal waking
hours.
People adapt more rapidly if artificial light is kept bright in the
workplace and if the bedroom is kept dark
Melatonin at appropriate time (just before going to bed)
reduces the adverse effects of jet lag and shift work
Also improved sleep of blind people
• light cannot serve as a zeiteber