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Sleep and Arousal: NRS201S John Yeomans
Sleep and Arousal: NRS201S John Yeomans
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 (Ch1-
4).
Norepinephrine and Serotonin
No rhythm
to SCN.
• Provide input to pretectal nucleus for
pupillary reflex.
• Provide input to intergeniculate leaflet of
thalamus. IGLSCN.
• 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
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