Chapter 9b final - Memorial University
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Transcript Chapter 9b final - Memorial University
Copyright © Allyn & Bacon 2010
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
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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
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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
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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