Basic Science And Sleep Knowledge Flashcards
What are the 3 distinct states of the sleep system?
Wakefulness, NREM, REM
Ascending arousal systems in the brain stem and posterior hypothalamus, what are they?
pedunculopontine (PPT) laterodorsal tegmental (LDT) locus coeruleus (LC) tuberomammillary nucleus (TMN) substantia nigra (SN) ventral tegmental (VTA) basal forebrain (BF)
Wakefulness
excitatory neurons relay sensory input to the thalamus, hypothalamus, and basal forebrain and activate cortex to increase wakefulness; suppressed during sleep.
What are the Neurotransmitters and neuropeptides that modulate and influence wakefulness promotion?
Acetylcholine Histamine Dopamine Serotonin Norepinephrine
Acetylcholine, what stages is it present?
increased in wakefulness and REM sleep
Histamine,
what stage in the sleep system is it present?
Where in the brain is it released?
What is it’s main action?
Released from tuberomammillary nucleus (posterior hypothalamus) (TMN)
increased in wakefulness and very low in REM
histamine appears to be the major arousal-promoting neurotransmitter at wake onset
Dopamine
Where in the brain is it released?
What stages in the sleep system is it increased?
What is it’s main actions?
ventral tegmental area, substantia nigra, posterior hypothalamus, and brain stem
increased in wakefulness and very low in REM
more likely to promote wakefulness under conditions of motivation or physical activity
Serotonin
What part of the brain is it released from?
What stages in the sleep system is it present?
median and dorsal raphe
increased in wakefulness and very low in REM
Norepinephrine (NE)
Where in the brain is it released?
What stages in the sleep system is it present?
What is it primary actions?
locus coeruleus (midbrain)
increased in wakefulness and very low in REM
increased cortical activation, particularly under conditions of stress and in the presence of novel stimuli
what is hypocretin (also called orexin)?
A deficiency of Orexin is associated with what condition?
What functions is orexin linked to?
Neurons in the lateral or posterior hypothalamus that produce hypocretin (also called orexin) are also active during the wake state
Orexin is a peptide that projects to cortex and subcortical arousal systems to promote awake state.
Plays important role in stabilizing wakefulness and sleep
Neuropeptide that regulates arousal, wakefulness and appetite
deficiency of hypocretin/orexin primary etiology of EDS and cataplexy in narcolepsy.
Hypocretin/orexin function linked to control of feeding behaviors, locomotion, autonomic functions.
What is the ventrolateral preoptic area (VLPO)?
major sleep-promoting area located in anterior hypothalamus
controls REM and NREM sleep
During sleep (especially SWS) – VLPO neurons active, high firing rates.
VLPO is active during sleep, releases inhibitory neurotransmitters (GABA, galanin), which inhibit neurons of ascending arousal system that are involved in wakefulness and arousal.
VLPO activated by adenosine and prostaglandin D2 (somnogens).
VLPO inhibited during awake state by NE and ACH.
VLPO neurons send projections to where?
wake-promoting regions: tuberomammillary nucleus (TMN) locus ceruleus (LC) LDT and PPT these inhibitory neurons are believed to induce sleep by coordinating the inhibition of all the wake-promoting cholinergic and aminergic regions.
Most VLPO neurons release what neurotransitters?
inhibitory neurotransmitter g-aminobutyric acid (GABA) at their sites of projection
some utilize the inhibitory neurotransmitter galanin.
What controls REM sleep?
The control of REM sleep involves the interaction of brain stem cholinergic and aminergic neurons in a complex feedback loop
neurons releasing acetylcholine (LDT/PPT region) are disinhibited by the suppression of aminergic neurons (e.g., NE, histamine) during REM.
REM-associated muscle atonia is linked to?
inhibition or loss of excitation of motor neurons in the brain stem and spinal cord via the medulla
pathways originate in the LDT and PPT
involve neurotransmitters acetylcholine, glutamate, glycine
sleep effects of drugs, overview Benzos? antihistamines? TCA's and SSRI's Psychostimulants
sleep-promoting benzos enhance GABA signaling
antihistamines block histamine receptors
TCA’s and SSRI’s act as REM suppressants enhancement of aminergic signals
inhibition of REM-promoting neurons.
Psychostimulants promote wakefulness by increasing dopamine and NE signals
Suprachiasmatic Nucleus (SCN), what is this?
Located in anterior hypothalamus, behind eyes
Major circadian pacemaker in mammals, “master clock”
Controls rhythms of CBT, sleep/wake propensity
Controls secretion of melatonin, cortisol
SCN function helps maintain alertness, alerting signal during the day, reduced signal at night
Zeitgebers entrain SCN to physical environment
Human Alertness What is the circadian dip and when does it occur? What is. The second wind phenomenon? When is the peak of alertness When is the lowest levels of alertness?
Midday decrease in alertness 2-4pm, circadian dip
Alertness peaks in early evening hours
“Second wind” right before circadian signal drops off for sleep
lowest levels of alertness occurs 4-6am
What are Zeitgebers?
Time givers (German)
External stimuli, environmental cue
Entrain the SCN to the physical environment, light-dark cycle
circadian rhythms are actually longer than 24 hrs, intrinsic clock is “entrained” by Zeitgebers
Most potent is sunlight
Other: exercise, food, social activities
In the absence of zeitgebers, circadian rhythms are desynchronized or “uncoupled” from one another “free-running”)
Other types: feeding, social, exercise, cognitive activities (work)
Circadian rhythm in humans?
Period of the rhythm is called tau
Mean value of the rhythm in humans=24.2 hrs
To maintain synchrony with light/dark cycle, external stimuli induce slight daily advance to counteract intrinsic phase delay
Zeitgebers (esp.sunlight) entrain the clock
What are markers of Circadian Phase?
CBT min (core body temp, minimum) DLMO (Dim light melatonin onset)
CBT min, when does it occur?
2-3 hrs before spontaneous awakening from unconstrained nocturnal sleep
(4-5 am in most individuals)
Reduction in CBT during sleep period corresponds to elevation in plasma melatonin
DLMO, when does it occur?
How is it measured
DLMO occurs ~2 hrs before habitual sleep onset
Determined by interval measurement of salivary or plasma melatonin performed in dim light (5 lux) in the evening
Light inhibits melatonin secretion
How to estimate CBT min?
Can be estimated as DLMO + 7 hrs
Phase Shifting by Light
Light exposure before the CBTmin causes phase delay.
Light exposure after the CBTmin causes a phase advance
Normal light exposure during early am induces daily phase advance in circadian rhythms to compensate for intrinsic tendency to phase delay due to tau longer then 24 hrs.
Common light exposures
bright blue midday sky >100,000 lux Sunrise or sunset ~10,000 lux commercial light boxes up to 10,000 lux normal room light ~200 lux moonlight 0.1 lux
What are intrinsically photosensitive retinal ganglion cells (IPRGCs) ?
circadian photoreceptors
entry point for light/dark information into the circadian system
IPRGCs send excitatory input to SCN via retiino-hypothalamic tract (RHT)
What is the retinal hypothalamic tract?
monosynaptic pathway from eye to SCN
What is an epoch
An epoch is how sleep is staged on PSG
Sleep is staged in 30 second epochs
How is stage REM detected?
EOG (eye movement) and Chin EMG are used to detect Stage R
REMs are noted
Decreased muscle tone
Decrease in chin EMG amplitude during stage R
What are the stages of sleep?
Wake, Stage W Stage N1 (light) Stage N2 (spindle, K complex) Stage N3 (SWS, Delta) Stage R (REM)
What happens without sleep?
Can’t maintain pathways in brain that let you learn and create new memories
Everyone needs sleep, but its biological purpose remains a mystery
Quality sleep is as essential to survival as food and water
What is melatonin?
Hormone that helps regulate sleep timing, “dark hormone”; need to start falling asleep
Produced in pineal gland
Inactive during the day and switches on around 9pm
Melatonin itself doesn’t make you fall asleep; it just tells your body that it’s time to fall asleep.
Lowers alertness and decreases CBT
Works in tandem with circadian clock, let’s you know when you should rest and when you should be awake.
What is the impact of light exposure on melatonin?
Too much light exposure at night; delays release of melatonin
How would you use melatonin for trouble falling asleep?
Take melatonin 5mg 60 min. Before bedtime for trouble falling asleep.
Take before usual bedtime and same time every day
What is an ultradian cycle
Sleep cycle of typically 90-100 min. In adults
Typically NREM sleep followed by period of REM sleep
Usually 3-5 NREM/REM cycles occur per night, each lasting 90-100 min.
What is sleep latency and what is normal in an adult
SL is time to fall asleep after lights out
SL should be less than 30 min, typically about 15 min.
SL increases with age slightly
Patients with sleep onsent insomnia have SL >30 min.
What is a hypnogram?
Plot of sleep stage vs time of night
What is WASO?
Wake after sleep onset
What is the typical sleep pattern for 20 year old?
Stage N1: 5% Stage N2: 45% Stage N3: 20% Stage R: 25% Arousal index (#/hr): 5-10
What is typical sleep pattern for 60 year old?
Stage N1: 15% Stage N2: 55% stage N3: 10% Stage R: 20% Arousal Index (#/hr): 15-20
How does sleep change as we age?
TST and SE decrease with age, esp after age 50
Amount of wake increases with age (WASO)
SL increases with age
When does napping stop for children?
Napping in children uncommon after age 7
Daily napping uncommon after age 5
What is the normal ultradian cycle in children?
In children, sleep cycle duration is 45-60 min.
Greater number of NREM/REM cycles per night compared to adults
How do infants enter sleep?
In infants, entry via REM sleep (active sleep) is common
How do adults enter into sleep?
Adults enter into sleep from wakefulness via NREM (usually stage N1)
What is the purpose of REM sleep?
REM sleep provides brain form of overnight therapy
Helps process difficult emotional experiences
Heightened levels of anxiety during the day can disturb sleep
What is the impact of anxiety on sleep?
Heightened levels of anxiety during the day can disturb sleep.
Anxiety prevents falling/staying asleep
Activates sympathetic nervous system, “fight or flight”
“ A ruffled mind makes a restless pillow”, C. Bronte
What is the typical sleep duration in adults?
Most of us get 7-8 hrs sleep
1/3 of population gets 6 hrs or less
Nocturia and sleep
Nocturia disrupting sleep increases with age
Increases after age 50
Impacts equally men and women