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