Neuroscience - Sleep and Narcolepsy Flashcards
What are the 4 different sleep stages?
1) Awake
2) Drowsy
3) NREM
4) REM
How many stages of NREM slep are there?
4
Describe the EEGs of all sleep stages (wave patterns)
1) Awake - low voltage, fast beta waves
2) Drowsy - alpha waves
3) Stage 1 NREM - theta waves
4) Stage 2 NREM - theta waves with intermittent spindles and k-complexes
5) Stage 3&4 NREM - Deep (slow-wave) sleep - delta waves
6) REM (dream) sleep - low voltage, random, fast, mixed frequency with saw-tooth waves
Increased heart rate, respiratory rate and head movements all coincide with what stage of sleep?
REM
For wake, NREM ad REM sleep, describe the sensation and perception, thought and movement
Wake:
- vivid, externally generated
- logical, progressive
- continuous, voluntary
NREM:
- Dull or absent
- Logical, repetitive
- Episodic, involuntary
REM:
- Vivid, internally generated
- Illogical, bizzare
- commanded but inhibited
What are the 3 distinct groups of neurons that promote wakefullness and sleep?
Wake active: monoaminergic neurons (noradrenaline, serotonin, histamine) in the brain stem and hypothalamus
Sleep-active: GABA-ergic neurons in the hypothalamus
REM-active: Cholinergic neurons in the brain stem
How do, wake, sleep and REM active neurons work?
Wake-active: promote wakefulness by directing excitatory effects on thalamocortical neurons and inhibition of sleep-active neurons
Sleep-active: promote sleep by inhibiting wake-active neurons
REM-active: activity rises and declines periodically during sleeping
What are Orexin and hypocretin and what are their receptors?
- Peptides
- Hypocretin found in hypothalamus
- Bind to G-protein couples receptors
- Hypocretin 1 to HcrtR1
- Orexin A to OX1R
What circuit controls wake-active and sleep-active?
FLIP-FLOP circuit
How does the flip-flop circuit work?
- Acts like a seesaw to prevent intermediate states
- Reciprocal inhibition between the groups
- Neuronal input on either site controls sleep and wakefulness
What 2 processes drive sleep?
1) Sleep homeostasis
2) Circadian rhythm
How does sleep homeostasis control sleep?
- Sleep deficit accumulates
- Sleep-promoting substances such as adenosine build up and act to inhibit wake neural pathways
How does caffeine keep you awake?
Caffeine acts as a adenosine receptor antagonist to promote wakefullness
How does circadian rhythm control sleep?
Endogenous rhythm due external factors such as daylight
What are the characteristics of circadian rhythm?
- Endogenous rhythm of 24 hours
- Generated by a master clock in neurons of the superchiasmatic nucleus (SCN) of the hypothalamus
- Rhythm is synchronised by time setters, notably the light-dark cycle
- Secondary or slave clocks present in several peripheral organs e.g heart, intestines, and coordinated by the master clock
What happens to molecular signals in the clock neurons?
Transduced into electrical signals that are transmitted to other regions of hhypothalamus and brain to regulate feeding, locomotion, temp, hormone secretion, sleep-waking etc
What are “morning larks” and “night owls”
People we have slightly shifted circadian rhythm (up to ~2 hours)
Give an example of a sleep disorder involving a bigger shift in circadian rhythm
Familial Advanced Sleep Phase Syndrome (FASPS)
early wake and inability to stay up at night
What are the symptoms of insomnia and what are the causes?
- Inability to sleep for adequate periods
- Stress, jet-lag, caffeine, shift work, depression
What are the treatments for insomnia?
Lifestyle changes
Sleep-promoting medication
What are the characteristics of narcolepsy?
- Inability to stay awake (sleep attacks - 30 secs to 30 min duration)
- Cataplexy - loss of muscle tone without loss of consciousness - in about 70% of narcolepsy patients
- Normal sleep disturbances
- Dream-like hallucinations at wake-sleep or sleep-wake
- Sleep paralysis
What molecule is reduced/absent in narcolepsy patients?
Orexins
What experimental evidence is there for this?
- Dramatic reduction in the cerebrospinal fluid in narcoleptics
How does orexin maintain wakefulness?
Provides excitatory effects on the wake-active neurons (flip-flop switch in wake position)
How does loss of orexin function cause the symptoms of narcolepsy?
- Sudden transitions between wake and sleep due to unstable switch
- Cataplexy (REM-like state) due to loss of wake-active inhibition of REM-active neurons
How many cases of narcolepsy are due to orexin deficiency?
Very few in humans
What are the 2 main risk factors for narcolepsy?
1) Susceptibility genes: most associated with immune system
- Class II HLA - mutant allele found in 98% of narcoleptics
- T cell receptor and others
2) Infectious agents
- Upper airway infection by streptococcus pyogenes and influenza A
What is the most likely explanation for the majority of narcolepsy cases?
Autoimmune attack on orexin neurons
What are the current treatments for narcolepsy?
- Amphetamines - promote wakefulness by raising monoamine transmitter levels
- Ticyclic anti-depressants, MAO inhibitors, SSRIs - to treat cataplexy
- Benzodiazepines - seditive to aid night time sleep
What are the potential future treatments for narcolepsy?
- Orexin-replacement therapy
- Stem cell replacement
