Sleep Cycle Pathophysiology

Question 1

Define Sleep

Answer 1

Unconsciousness from which a person can be aroused by sensory or other stimuli

Question 2

Define Coma

Answer 2

Unconsciousness from which a person cannot be aroused

Question 3

For those 65 y.o or olders,

Answer 3

80% report sleep-related disturbances

Question 4

Electroencephalogram

Answer 4

Monitors state of sleep

Uses scalp electrodes to monitor electrical signals produced by the surface of the brain

Question 5

If they stimulate the ascending activating system,

Answer 5

You wake up

Question 6

If they stimulate the thalamus,

Answer 6

You fall asleep

Question 7

What happens during sleep?

Answer 7

Brain cleans itself
Waste products of brain metabolism are removed from the interstitial space among brain cell where they accumulate
- Faster clearance during sleep as compare to awake

Question 8

What happens if you don’t sleep?

Answer 8

Potentially toxic metabolites that are there as a result of a working brain won’t be cleared

Question 9

Phases of Sleep

Answer 9

First Non-Rapid Eye Movement sleep (NREM) and then shift to REM sleep
- Typically 4-6 cycles of REM and NREM (each night with each cycle lasting 90 minutes)

Question 10

Define REM

Answer 10

Active or desynchronized sleep

Question 11

Define NREM

Answer 11

Quiet, restful, or slow wave sleep

- Dreamless sleep

Question 12

*Stage 1 of NREM

Answer 12

Between the state of awake and sleep
Background theta waves
- Where you get the falling sensation

Question 13

*Stage 2 of NREM

Answer 13

Background theta waves superimposed with burst of sleep spindles and K complexes
- Longest portion

Question 14

*Stage 3 of NREM

Answer 14

*Slow wave or delta sleep
Reduction in brain and body temperature
*Eye movements are absent and muscle tone is very low
Reduced BP, HR, RR, cortisol and thyroid hormone levels, increased growth hormone

Question 15

REM Sleep last for how long

Answer 15

5-30 minutes

25% of total sleep

Question 16

REM Sleep is characterized by:

Answer 16

Low amplitude, mixed frequency, desynchronized EEG activity (similar to awake state)
Brain is activated
*Burst of bilateral eye movements, active dreaming and fluctuations in RR and HR
Gets longer throughout the night

Question 17

Sleep in Newborns

Answer 17

18-20 hours of sleep per day with poor segregation between REM and NREM
Start in REM and NREM is only ~50 minutes

Question 18

By 3 years old, sleep

Answer 18

Segregate sleep and wakefulness into distinct periods

Question 19

Sleep in Adolescence

Answer 19

Reduced slow wave delta sleep

Question 20

Sleep in Older age

Answer 20

Reduction in length of sleep and increase in number or awakenings
Reduced slow wave delta sleep
Fall asleep earlier and wake up earlier

Question 21

Ascending Reticular Activating System (ARAS) involves what neurotransmitters?

Answer 21

Adrenergic (NE)
5HT
DA
Histamin

Question 22

ARAS promotes:

Answer 22

Wakefulness and arousal through inhibition of cholinergic cells that promote REM sleep through NE and 5HT

Question 23

Ventrolateral Preoptic Area (VLPO) involves what neutrotransmitters?

Answer 23

GABA

Question 24

VLPO promotes

Answer 24

Sleep through neuron firing that decreases ARAS activity

Question 25

Orexin/Hypocretin Peptide System promotes:

Answer 25

smooth transition from awake to sleep or vice versa | - Located in the lateral hypothalamus (LAT)

Question 26

How does NREM sleep get initiated?

Answer 26

Driven by VLPO GABAergic neurons which are active during sleep and inhibit TMN histaminergic neurons and (NE, DA, 5HT)

Question 27

Sleep and Wake Promoters

Answer 27

When the TMN is active and histamine is released, the wake promoter is on and sleep promoter is inhibited When VLP is active and GABA is released in TMN, the sleep promoter is on and the wake promoter is inhibited

Question 28

How is REM sleep initiated?

Answer 28

During NREM sleep, VLPO neurons start to inhibit orexin neurons (which normally excites REM-off NE and 5HT cells) So, VLPO inhibits REM-off monoamineric cells which disinhibits REM-on cholinergic cells of the pontine tegmentum

Question 29

Pontine tegmentum cholinergic cells also:

Answer 29

Project to medulla and spinal cord to initiate many of the physical manifestations of REM sleep (muscle atonia, eye movement)

Question 30

**What cells promote REM-on and are inhibited during wakefulness?

Answer 30

Pontine tegmentum (PPT and LDT) Cholinergic Cells

Question 31

Sleep + homeostatic drive?

Answer 31

Partially controlled Related to the length of prior wakefulness Drive increases throughout the day MOA is poorly understood but involves adensosine**

Question 32

Adenosine function

Answer 32

May modulate the sleep generating effect

Question 33

Carreine and methylxanthines function

Answer 33

Block adenosine receptors to promote activity and attention

Question 34

Circadian Rhythm Function and how it does it?

Answer 34

Sleep regulation | Controlled by Suprachiasmatic nucleus (SCN)

Question 35

What is the SCN and how does it work?

Answer 35

Primary pacemaker of neuroendocrine phythms | Direct neural input from the retina to the SCN allows the SCN to be closely linked to light and dark cycles

Question 36

Circadian + Homeostatic

Answer 36

Circadian: wake drive comes from input (light, melatonin, activity) to the SCN Homeostatic: sleep drive increases the longer one is awake and decreases with sleep - As the day progress, circadian wake drive diminishes and homeostatic sleep drive increases until the VLPO sleep promtor triggers the release of GABA and TMN inhibits wakefulness

Question 37

Excessive arousal during the day leads to

Answer 37

Hyper-vigilance during the night which leads to insomnia

Question 38

Deficient arousal during the day leads to

Answer 38

Excessive sleepiness and sleep attacks

Question 39

Cortico-Thalamic Circuit does what?

Answer 39

Thalamus has a critical role in regulating arousal by controlling amount of sensory input that reaches the cortex

Question 40

Sleep/wake disorders = problem with:

Answer 40

Thalamic filters -

Question 41

Insomnia + Thalamic FIlters

Answer 41

Filters fail to filter out sensory input in the cortex at night - Boost the filter with GABA-enhancing agents

Question 42

Daytime sedation + Thalamic FIlter

Answer 42

Filters filter out too much sensory input to the cortex during the day - Reduce the filter with DA agents or stimulants