Physiology of sleep

Question 1

Compensation following sleep loss

Answer 1

sleep more after sleeping less

homeostatic drive likely due to adenosine buildup.

Question 2

Why do we sleep?

Answer 2

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

Question 3

Different kinds of light as cues for our body

Answer 3

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

Question 4

Hormonal and peptide rxn to light

Answer 4

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

Question 5

Disorders of arousal

Answer 5

walking, terrors, confusional arousal, night eating syndrome

usually arise early out of N3, SWS

Question 6

REM sleep behavior disorder

Answer 6

usually arises later, out of REM sleep

Question 7

Normal latency to REM (and disorders associated with short latency to REM)

Answer 7

~90 minutes.

Short REM latency seen in depression, alcohol withdrawal, very short seen in narcolepsy.

Question 8

Adenosine

Answer 8

Basal Forebrain

accumulates during wake

reduced during sleep

blocked by caffeine

Question 9

Sleep/wake switch

Answer 9

mediated by the hypothalamus

clusters of neurons that use GABA, histamine, and hypocretin as neurotransmitters

Question 10

suprachiasmatic nucleus

Answer 10

Circadian clock modulates alertness,
Core body temperature (CBT), cortisol and
Melatonin secretion

Question 11

Ascending cortical activation, REM/SWS switch

Answer 11

Brainstem

aminergic and cholinergic neurons

Question 12

Thalamus and sleep

Answer 12

Gate to the cortex

Spindles, slow wave sleep

Question 13

NREM sleep physiology

Answer 13

Neurons of the ventrolateral preoptic area (VLPO- GABA and galanin) inhibit the arousal systems

Question 14

REM sleep physiology

Answer 14

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.

Question 15

Hypocretin neurons

Answer 15

lateral hypothalamus; arousal, wakefulness, appetite

Active when awake

Off during NREM sleep

Some active during REM?

Question 16

Homeostatic drive S

Answer 16

The longer we are awake, the sleepier we get

Mediated by adenosine

Question 17

Circadian alerting system (C)

Answer 17

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

Question 18

Melatonin production and release

Answer 18

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.

Question 19

When do we sleep best and worst in term of core body temp (CBT)?

Answer 19

Best on downslope

Worst on upslope

Question 20

Delayed sleep phase syndrome

Answer 20

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.

Question 21

Advanced sleep phase syndrome

Answer 21

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.

Question 22

Obstructive sleep apnea

Answer 22

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

Question 23

Two major types of insomnia

Answer 23

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.

Question 24

Restless Legs Syndrome

Answer 24

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”)

Question 25

Narcolepsy

Answer 25

Lesions in hypocretin system, a disease characterized by loss of boundaries between sleep and wakefulness.

Treat with naps, stimulants, sodium oxybutyrate