Week 4 - Chronobiology Flashcards

1
Q

what does a normal sleep cycle consist of? how long is it?

A

Light sleep: Stage 1 = 6%, 2 = 49%
Deep sleep: Stage 3/4 = 23%
Dream sleep: REM = 22%

cycles are 90 minutes, that go from wake –> 1 –> 2 –> 3 –> 4 –> 3 –> 2 –> REM –> 2…
-there may be brief arousals from stage 1 that are not remembered

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2
Q

what happens to the REM and stage 4 amount throughout the night?

A

REM increases as stage 4 lessens

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3
Q

what is an EEG?

A

electroencephalogram; measures cyclic predictable pattern

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4
Q

what is seen during wakefulness on an EEG, for both alert and “drowsy”

A

alert: low-voltage, fast, random activity with high frequency beta waves
drowsy/relaxed: low voltage, fast, random activity with alpha waves

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5
Q

what does the EEG show for the 4 stages of non-REM (NREM) sleep/

A

1: lightest sleep, high frequency, low voltage with theta waves
2: light sleep with sleep spindles and K complexes
3: deep/slow wave sleep, synchronous delta waves
4: deepest sleep, delta waves >50%

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6
Q

what happens during stage 4 NREM?

A

deepest sleep, parasympathetic control, lowered vital signs, restorative sleep

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7
Q

what happens during in REM sleep? what does the EEG look like?

A

desynchronized, paradoxical, activated

  • low voltage, high frequency, random, fast sawtooth waves
  • EEG appears awake
  • paralysis and dreams occur
  • eyes move and erections occur
  • sympathetic tone dominates
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8
Q

how many hours of sleep has the soonest mortality?

A

short sleepers: 8 hours

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9
Q

how does sleep length change as we age?

A

III/IV (deep sleep) decreases while I/II (light sleep) increases

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10
Q

what does melatonin do for sleep chemistry? what receptors does it stimulate?

A

made in the pineal gland at night due to a loss of light-induced neuronal firing in retinohypothalamic tract

  • stimulates MT1: lower brain activation/arousal (turns off midbrain and suppresses sympathetic)
  • stimulates MT2: facilitates 24 hr circadian clock
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11
Q

what does cortisol do for sleep chemistry?

A

peaks in the morning (4-5 AM) linking the HPA (hypothalamic-pituitary axis) to the circadian system

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12
Q

what is the reticular formation (ascending reticular activating system)?

A

runs through core of brainstem from medulla to midbrain to posterior hypothalamus

  • “monolithic” system that incorporates systematic input from many entities that cause arousal
  • -ACh, glutamate, monoamines (NE, DOPA, SE, His)
  • -these act directly on certain brain areas and modulate other transmitters’ effects, and allow amplification of arousal signals
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13
Q

what are the 6 nt that make up the RAS?

A

ACh, glutamate, and the monoamines (norepinephrine, dopamine, serotonin, histamine)

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14
Q

how is ACh involved in waking? what makes it? when is it active? what does it do?

A

made in basal forebrain, and active during wakefulness and REM

  • in pons, the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT)
  • from these, project to sub-cortical regions like thalamus, lateral hypothalamus, then back to basal forebrain
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15
Q

how is it that the basal forebrain can promote wakefulness and lower sleepiness?

A

ACh is active during wakefulness (most robustly via projection to thalamus) and REM
GABA inhibits inhibitory neurons in sleep promoting centers, meaning that sleep drive is diminished

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16
Q

how is NE involved in waking?

A

made by locus coeruleus under 4th ventricle

  • neurons fire during wakefulness, less during NREM and none during REM
  • optimizes attention and task performance while awake
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17
Q

how is NE involved in insomnia/anxiety? what is it inhibited by?

A

excessive firing causes insomnia and anxiety at night (anxious and worried at bed time)

inhibited by alpha-1/2 receptors in a feedback loop
-use BP medications to lessen nightmares and anxiety

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18
Q

how is histamine involved in waking? what receptors does it bind to?

A

made in tuberomammilary nucleus in posterior hypothalamus

  • increased firing when awake > NREM > REM
  • H1 receptors –> wakefulness
  • H3 autoreceptors –> inhibit histamine activity
  • -blocking/antagonizing H3 receptors promote wakefulness
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19
Q

how is serotonin involved in waking? which receptors increase wakefulness? which blocking drugs promote NREM or promote/correct circadian rhythms?

A

there are 15 different receptors, so sometimes will wake or sleep

  • serotonin supply is the dorsal raphe
  • generally promotes wakefulness and inhibits REM (stimulate 5HT1a,1b,2,3)
  • drugs that block 5HT2 promote NREM
  • drugs that block 5HT1D and 5HT7 promote/correct circadian rhythms
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20
Q

how is dopamine involved in waking?

A

made in substantia nigra (promotes movement) and ventral tegmental area (reward)

  • ventral periaqueductal gray in pons fires durign wakefulness
  • provides motivational arousal as opposed to task oriented alertness
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21
Q

how is orexin/hypocretin involved in waking? what happens if you don’t have it?

A

NOT part of RAS, but rather innervates and controls all other wakefulness areas

  • excitatory neuropeptides orexin A/B made in lateral hypothalamus as wakefulness regulators
  • fire only when awake, not in NREM or REM
  • sustain wakefulness when other systems falter
  • if missing this, will go to sleep randomly
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22
Q

how is the thalamus involved in waking?

A

all of RAS is coordinated/gated via thalamic relay tracts/systems
-brain stem arousal center info must go thru thalamus to arouse cortex to wakefulness

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23
Q

what do glutamatergic VS GABAergic neurons do?

A

glutamatergic neurons - facilitate cortical arousal

GABAergic neurons - dampen ascending arousal pathways when sleep is needed

24
Q

how is the thalamus involved in sleep? how is this related to ACh?

A

sleep spindles originate in thalamus, signifying that during NREM thalamic neurons are hyperpolarized and decrese responsiveness to external stimuli and synchronous SWS/delta occurs
-during wakefulness and REM, ACh input depolarizes the same neurons, increasing arousal and awareness causing desynchronous firing

25
Q

how does the reticular activating system act as a dimmer?

A

operates by incrementally increasing NE, DA, SR, ACh

  • may go from 0 to 150%
  • can manipulate faltering system with stimulants, TCAs, SNRIs, NRI, NDRIs
26
Q

how does the TMN (histamine) and VLPO (sleep center) act as simple switches?

A

operates in bipolar, all-or-none fashion by facilitating histamine or GABA/galanin

  • may be either 0 or 100%
  • is a slave to the SCN (suprachiasmatic nucleus) master switch
  • can manipulate faltering system with modafinil, armodafinil
27
Q

what is a “faltering system” for wakefulness?

A

fatigue, sleepiness, inattention, executive dysfunction

28
Q

how does the orexin/hypocretin system act as a backup generator?

A

operates by incrementally increasing orexin

  • may go from 0 to 100%
  • innervates dimmer (reticular activating system) and the switch (TMN and VLPO)
  • manipulate faltering system with modafinil, armodafinil (like TMN/VLPO)
29
Q

what is needed in order to sleep?

A

ventrolateral and median preoptic areas (VLPO/MNPO) of lateral hypothalamus are “off” switch and NREM promoting center of CNS

  • causes sleep via increased GABA and galanin activity
  • turns off histamine-based TMN wakefulness half of the switch
  • IOW: VLPO/MNPO are silent during wakefulness, but fire rigorously during NREM
30
Q

when do MNPO VS VLPO fire? what do they contain?

A

MNPO fires as one drifts to sleep, while VLPO fires while asleep (to maintain it)
-both have GABA and galanin inhibitory transmitters with fibers projecting to arousal centers

31
Q

how is REM sleep controlled?

A

by laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) ACh firing

  • allows desynchronized firing similar to wakefulness
  • provides atonia by stimulating neurons in medulla that release GABA and glycine into spinal motor neuron tracts
32
Q

how does 5HT, NE, DA, and ACh interact during NREM? during REM?

A

NREM: they all fire to some degree, suppressing ACh to allow process of sleep staging 1–>4 throughout the night
REM: ACh peaks and feedback inhibits the others

33
Q

how can you wake up without the alarm?

A

RAS has woken us up

34
Q

what does adenosine homeostasis have to do with sleeping?

A

increases while awake during metabolism (ATP breakdown)

  • adenosine buildup is governed by astrocytes and yields inhibitory feedback to wakefulness centers, and stimulates VLPO sleep center so sleep occurs
  • once concentrated enough, we fall asleep, and recover ATP
35
Q

what are somnogens and how do they work?

A

cytokines IL-1B, TNF-alpha from brain parenchyma and promote sleep

  • all increase in the evening, inhibiting arousal centers
  • prostaglandin D2 is made in the meninges and promotes NREM
36
Q

what is the circadian clock?

A

lack of light via eyes/optic nerve signals suprachiasmatic nuclei of hypothalamus to allow melatonin release

  • can suppress melatonin with 24 hour light
  • melatonin can drive circadian 24 hour rhythm as well
37
Q

what controls the circadian clock? how do they fluctuate? what can affect these?

A

genes and proteins (CRY, CLOCK, BMAL1, PER1/2/3

  • these genes make clock go faster/slower or be synchronized
  • some fluctuate on a 24-hour basis
  • -based on the time it takes for the genes to turn on, make enough PRO to trigger the next cascade
  • -time it takes to transcribe and translate creates the 24 hour clock
  • can be affected by light and temperature
38
Q

how are BMAL1 and PER1/2/3 related? what do PER2 and CRY do?

A

BMAL1 and PERs are in counterphase
PER2 positively enhances BMAL1 system
CRY negatively enhances PER and CRY loops

39
Q

what are Zeitgebers?

A

exogenous melatonin, caffeine, alcohol, light, food, exercise/activity, and social interaction
-they all can modify or override our clock

40
Q

what are the components of sleep drive, versus circadian alerting signal?

A

sleep drive: adenosine, clock genes, GABA, galanin

circadian alerting signal: NE, DOPA, SR, orexin, histamine

41
Q

what is insomnia? how is it treated?

A

difficulty initiating or maintaining sleep, early morning awakening, or non-restorative sleep for one month

  • next day consequences
  • no organic, psychologic, substance etiology
  • treat with sleeping pills (block anti-histamine) or sleep hygiene
42
Q

what causes something to be a disorder?

A

only a disorder if it messes with one’s life

43
Q

what happens to brain activity with sleep deprivation?

A

obvious decrease in brain activity, particularly in frontal cortex

44
Q

what is hypersomnia? how is it treated?

A

excessive daytime sleepiness or inability to maintain wakefulness

  • next day consequences
  • no organic, psychological, substance etiology
  • treat with stimulants and wakefulness hygiene
45
Q

what is narcolepsy? what does cataplexy and hyponogic mean? how is it treated?

A

daily sleep attacks over 3 months

  • cataplexy/hypnopompic (muscle weakness) upon awakening
  • hyponogogic hallucinations (upon sleeping)
  • no organic, psychological, or substance etiology
  • almost no REM latency (goes into instant REM)
  • sleep paralysis is common
  • treat with stimulants and a 20 minute nap every 2 hours
46
Q

what are breathing related sleeping disorders, and how are they treated?

A

central and obstructive apnea, that yield insomnia or hypersomnia

  • treat by avoiding sedatives, use CPAP mask, dental devices, or surgery (ineffective)
  • NEVER give GABA or alcohol, b/c would decrease breathing
47
Q

why is snoring a protective factor?

A

snoring will startle you to wake you up so you can breathe

48
Q

what is circadian rhythm sleep disorder? what is the difference between the advanced or delayed type? how to treat it?

A

yields insomnia or hypersomnia due to sleep-wake cycle mismatch, shift, or synchrony

  • advanced: in elderly; fall asleep too early at night, wake up too early in the morning
  • delayed: jet lag, shift work; fall asleep too late, and wake up too late
  • treat with sleep scheduling, benzodiazepines, melatonin, exercise, stimulants, or light therapy
49
Q

what are examples of dyssomnia NOS (not otherwise specified)? how are they usually treated?

A
  • nocturnal myoclonus - unconscious leg movements (periodic limb movement)
  • restless leg syndrome - creeping sensnations, conscious movement occurs
  • often treated with dopamine (D2) receptor agonists
50
Q

what is nightmare disorder? when does it occur? how is it treated?

A

mostly in kids; long, frightening dreams

  • awake, alert, and oriented afterwards
  • remember the dream
  • occurs during REM
  • self-limiting, no treatment
51
Q

what is sleep terror disorder? when does it occur? how is it treated?

A

mostly in kids; awake but disoriented, non consolable (scream and flail around, but not really “awake”)

  • no memory of it
  • happens in the first 1/3rd of the night during NREM stage 3/4
  • self-limiting, no treatment
52
Q

what is sleepwalking disorder? how is it treated? when does it happen?

A

somnambulism (can be caused by sleeping pills)

  • happens in first 1/3 of night during NREM 3/4
  • no memory, may awake confused but orients easily
  • self limiting
53
Q

what is sleep related bruxism? when does it happen? how is it treated?

A

teeth grinding during stage 2

-treat with mouth guard/bite plate

54
Q

what is REM sleep behavior disorder? how is it treated?

A

loss of atonia during REM, which usually doesn’t happen

  • men typically act out dreams, often violently (can hurt people sleeping next to them)
  • treat with D2 agonists (like for restless leg syndrome)
55
Q

what is sleeptalking? when does it occur?

A

somniloquy

  • happens in all stages of sleep
  • self limiting
56
Q

what is sleep paralysis?

A

inability to move just prior to fallign asleep or awakening

-self limiting