Transcript Sleep and Arousal

Sleep and Arousal
Lecture 9
NRS201S
John Yeomans
EEG Changes in Sleep
• Waking: Alpha (10 Hz) and beta/gamma
waves (40 Hz).
• Slow-Wave sleep: From alpha to spindles
(14 Hz) and delta (1-4 Hz).
• REM sleep: Cortical arousal and muscular
atonia. Also called paradoxical or dream
sleep.
• Triggered in pontine reticular formation.
Gamma
Alpha
Hours
REM Sleep
• Brain is active, and eyes are active.
• Muscles of body are profoundly inhibited
(atonia).
• Subjects report dreams, when awoken.
• NE and 5HT neurons silent. Ch neurons
active.
• In slow-wave sleep, brain and eyes are
quiet, but muscles are more active.
Transection studies
Brain Areas--Early Studies
• Coma (prolonged unconsciousness) due
to injury in dorsal reticular formation.
• Stimulation of RF leads to arousal.
• Ascending path for cortical arousal.
• Descending path for atonia.
• Critical area in dorsal pontine reticular
formation.
Diffuse Arousal Systems
• Locus coeruleus Norepinephrine neurons
(A6).
• Mesopontine Cholinergic neurons (Ch5,6).
• Raphe Serotonin neurons (B5,6).
• Tuberomammilary Histamine neurons.
• Lateral hypothalamus Orexin/Hypocretin
neurons.
• Basal forebrain Cholinergic neurons (Ch14).
Norepinephrine and Serotonin
Active in Waking and in Slow-Wave Sleep
Mesopontine Ch5,6
Basal Forebrain Ch1-4)
Cholinergic Arousal Systems
Active in Waking and REM Sleep
Model of REM Sleep Systems
Sleep Disorders
• Insomnia (too little sleep).
• Sleep apnea (loss of breathing in REM,
too much atonia?).
• Narcolepsy/cataplexy (daytime sleepiness
and REM/atonia attacks).
• Triggered by arousal (e.g. laughing,
running).
• Due to loss of orexin/hypocretin neurons in
humans, or receptors in dogs and mice.
Narcolepsy
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Orexin 2 receptors lost in dogs (Mignon).
O/H neurons lost in humans.
O/H gene or receptors in mice.
O/H neurons active in waking arousal, and
needed to inhibit atonia.
• In narcolepsy, arousal can activate
REM/atonia neurons, if O/H signal is lost.
• Which neurons and how? Ch5,6?
Loss of O/H neurons:
Daytime sleepiness,
Cataplexy (atonia) induced
by arousal.
Circadian Rhythms
March 17, 2006
PSY391S
John Yeomans
Timing of Motivated Behaviors
• When is best season to feed and mate?
Seasonal periods of activity and breeding
based on availability of food. Based on
axis of earth around sun.
• When is best time of day to feed?
Diurnal/nocturnal to find food and avoid
predators. Based on earth’s rotation
relative to sun.
• Circadian clock built into all plants and
animals to help survival.
Measuring Rhythms in Hamsters
Rhythms
• Endogenous clock: Measured in constant
conditions, still 23-25 hr. “free running”
• Rhythm is lost when SCN lesioned in
mammals, or pineal gland in birds.
• Rhythm is restored by transplanting new
SCN. Period of donor SCN.
• Tau mutant hamster has 20 hr rhythm.
• Therefore, SCN is endogenous clock for
activity.
Free running 24.1 hr
No rhythm
Tau mutant SCN
19.8 hr rhythm of donor SCN
Ralph et al. 1990
Retinal Paths to SCN and IGL
Entrainment
• Entrainment by light, temperature, or
arousing stimuli.
• Photic entrainment in mammals due to
retinohypothalamic path to SCN.
• Rods and cones not needed for entrainment!
• Search for new receptors in ganglion cell
layer led to melanopsin.
• Melanopsin ganglion cells directly activated
by light, indirectly by rods and cones.
• Huge dendrites and receptive fields,
insensitive to light, but stable (no adaptation)
Projections of Melanopsin Neurons
• Melanopsin neurons provide most of input
to SCN.
• Provide input to pretectal nucleus for
pupillary reflex.
• Provide input to intergeniculate leaflet of
thalamus. IGLSCN.
• IGL needed for arousing inputs to clock.
Entrainment by Arousal
• Clock can be shifted by food, exercise,
footshock and sex.
• Allow animals to adjust rhythms to
biologically significant opportunities.
• Like light, shift can be up to 3 hours.
• Shifts depend on phase—Light shifts best
in dark phase, arousal shifts best in light
phase.
Intergeniculate Leaflet: Arousal
Shifts Circadian Rhythms
Cain et al. 2001
Arousal Shifts Circadian Rhythms
in Hamsters
* Arousal (footshock, exercise, reward)
Cain et al. 2001
Evolution of Retina?
• How could eye evolve? Greatest problem for
Cajal.
• Circadian clock with direct access to light.
• Light detectors, no spatial information—direct
input to clock.
• Eye cup—Spatial information, focussing, with
pupil and lens later.
• Dark and light vision (cones and rods) with
adaptation.
• Two eyeballs with muscles, for distance
perception and fast movements in space.
Non-photic entrainment:
IGL to SCN
SCN
Clock
?
Circadian Genes
• How does endogenous clock work?
• Clock mechanism found in plants, simple
animals and many body cells.
• Clock genes found in mutant fruit flies. How?
• Take the flies who fly at odd hours. Map genes.
• per: No rhythm, long rhythms, short rhythms.
• Tim, cry, dbt.
• Map genes onto 4 fly chromosomes.
• Study functions of proteins: PER, TIM, DBT.
Mutations Alter Rhythms in Flys
and Mice
• per, tim are needed for 24 hr rhythms.
• Mutations lead to short, long or no rhythm.
• dbt mutations alter enzyme, casein kinase,
leading to short rhythm in Drosophila.
• Homologous genes (per1-3, cry, tau) found
in mice and humans.
• Transcription factors Clock and Cycle start
each cycle. These are also regulated.
Clock Genes and Negative
Feedback
• per, cry genes transcribed in nucleus.
• Per, Cry proteins are translated in
cytoplasm.
• Per/Cry dimers inhibit Clock/Cycle
transcription factors in nucleus.
• Less Per, Cry less inhibition.
• New per, cry transcribed 24 hrs later.
• Tau gene makes a casein kinase that
degrades Per.
Molecular Model of Clock
Nonphotic input from
thalamus IGL?
Gene transcription
proteins
Negative feedback loop
Photic input
from retina