Physiology of sleep Flashcards
Compensation following sleep loss
sleep more after sleeping less
homeostatic drive likely due to adenosine buildup.
Why do we sleep?
brain and body regeneration (NREM sleep, N3 SWS) and brain development/memory (REM sleep).
Performance of learned motor tasks improve after sleep, but not after similar period of wakefulness
Improved performance correlates with increases in focal delta over involved cortex during sleep
REM sleep essential for the developing mammalian brain, but functions of REM sleep in adults uncertain
Stage 3-4 (delta), now N3 sleep may be involved in synaptic “pruning” and “tuning
Different kinds of light as cues for our body
We likely evolved to take advantage of morning blue-green light; the orange – red spectrum of late afternoon and evening does not have the same salutary effects
Hormonal and peptide rxn to light
Morning light increases:
cortisol [helps stress]
serotonin [impulse control]
GABA [calm]
dopamine [alertness]
Light modifies synthesis of:
FSH [reproduction]
Gastrin releasing peptide
Neuropeptide Y (NPY) [hunger]
TSH [metabolism]
Dark allows melatonin production – “the hormone of darkness
Disorders of arousal
walking, terrors, confusional arousal, night eating syndrome
usually arise early out of N3, SWS
REM sleep behavior disorder
usually arises later, out of REM sleep
Normal latency to REM (and disorders associated with short latency to REM)
~90 minutes.
Short REM latency seen in depression, alcohol withdrawal, very short seen in narcolepsy.
Adenosine
Basal Forebrain
accumulates during wake
reduced during sleep
blocked by caffeine
Sleep/wake switch
mediated by the hypothalamus
clusters of neurons that use GABA, histamine, and hypocretin as neurotransmitters
suprachiasmatic nucleus
Circadian clock modulates alertness,
Core body temperature (CBT), cortisol and
Melatonin secretion
Ascending cortical activation, REM/SWS switch
Brainstem
aminergic and cholinergic neurons
Thalamus and sleep
Gate to the cortex
Spindles, slow wave sleep
NREM sleep physiology
Neurons of the ventrolateral preoptic area (VLPO- GABA and galanin) inhibit the arousal systems
REM sleep physiology
Driven by cholinergic pedunculo-pontine and laterodorsal tegmental (PPT/LDT) neurons (which are inhibited by NE, 5HT, HA during wake and NREM)
Cholinergic neurons also produce atonia of REM sleep by activating the medial medulla, which inhibits motor neurons with glycine.
Hypocretin neurons
lateral hypothalamus; arousal, wakefulness, appetite
Active when awake
Off during NREM sleep
Some active during REM?
Homeostatic drive S
The longer we are awake, the sleepier we get
Mediated by adenosine
Circadian alerting system (C)
Sleepiness waxes and wanes under the influence of the circadian alerting system (C) thought to reside in the suprachiasmatic nuclei & linked to core body temperature
Melatonin production and release
Light information travels to the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract (RHT). The SCN signals the pineal gland via the superior cervical ganglion & inhibits the production of melatonin.
In the absence of light, inhibition is removed, melatonin is produced - the SCN reduces firing in the dark.
When do we sleep best and worst in term of core body temp (CBT)?
Best on downslope
Worst on upslope
Delayed sleep phase syndrome
Night Owls
sleep normally in tune with their clock
“insomnia” when trying to sleep at socially appropriate time or EDS when awakened for school or work before enough sleep & before alerting rhythms rise.
Advanced sleep phase syndrome
Larks
“want” to sleep and wake early. If remain awake to watch news, they still wake early and EDS; their early morning awakening misinterpreted as insomnia due to depression.
Obstructive sleep apnea
increased work of breathing from snoring, to upper airway resistance syndrome, to respiratory effort related arousals, to hypopneas to apneas
Increased stress leads to a pro-inflammatory response increasing risk of CVHD, stroke, HTN and pulmonary hypertension and can predict the development of depression
In kids may be one cause of attentional difficulties since tired kids get hyperactive and have decreased ability to concentrate and lead to wrong dx of ADHD
Two major types of insomnia
Learned and co-morbid
Learned: learned or conditioned based on “sleep worry”; hyperarousal
Co-morbid: due to medical, psychiatric, pain, OSA, restless leg, circadian rhythm problems, narcolepsy, substances, meds
Often, people with “secondary insomnia” develop the learned one as well. So, even if you treat the initial cause of sleeplessness, insomnia will persist because patients are “hyper aroused”.
Treat with sleep restriction and stimulus control.
Restless Legs Syndrome
insomnia or EDS or both
waking discomfort. Urge to move legs and/or arms, with onset or worsened by rest, usually at night, and somewhat relieved by movement. ? Associated with HTN
Get serum ferritin and undergo fe replacement if 55 or less (will be reported as “normal”)
Narcolepsy
Lesions in hypocretin system, a disease characterized by loss of boundaries between sleep and wakefulness.
Treat with naps, stimulants, sodium oxybutyrate
