Circadian and homeostatic control of sleep Flashcards
What are the behavioural criteria for sleep?
What other criteria are there?
Behavioural quiescence
Elevated arousal threshold
Homeostatically regulated
Electrical criteria (EEG)
Pharmacological criteria (sleep states/neurotransmitters)
Molecular criteria (changes in gene expression)
Why do we sleep?
What are possible reasons and which is the leading hypothesis?
We don’t know
Widespread among animals
while we sleep, we cannot eat, mate, protect against predators; thus, there must be evolutionary advantages which outweigh the disadvantages
Adverse effect (death) upon sleep deprivation
Possible functions:
Brain restoration?
Energy conservation?
Synaptic homeostatis?
Memory consolidation? (leading hypothesis)
Dreaming?
What does a polysomnograph record?
What are the sleep stages and what does a polysomnograph record in each case?
Electrooculograph (EOG) - eyes
Electromyograph (EMG) - throat/neck
Electroencephalograph (EEG) - brain
Sleep stages
Stage 1:
- EOG: slow eye movements (SEM)
- EMG: high relative amplitude
- EEG: dominant frequency is theta waves (4-8 Hz)
Stage 2:
- EOG: limited eye movements
- EMG: relative amplitude smaller than stage 1
- EEG: dominant frequency is theta waves, K complexes and Sleep spindles also seen
- K complex: burst of high amplitude, low frequency*
- Sleep spindle: burst of high frequency, low amplitude*
Stage 3/4:
- EOG: limited eye movements
- EMG: Relative amplitude smaller than stages 1-2
- EEG: Dominant frequency is delta (1-4 Hz) “SLOW WAVE SLEEP”
REM sleep
- EOG: Rapid eye movement (REM)
- EMG: smallest relative amplitude (muscle atonia)
- EEG: dominant frequency is theta
Also called paradoxical sleep as EEG is similar to a woke perosn
*
What are the functions of SWS and REM sleep?
SWS:
homeostasis (recovery as a function of wake)
Learning, memory, synaptic equilibrium
Growth hormone secretion
REM:
Circadian regulation
CNS maturation, synaptogenesis, memory
Physiological substrate of dreams
How do somnograms differ in children and young/older adults?
What is the hypothesis for these differences?
Children have more, longer deep sleep stages
Young adults have fewer, older adults basically have no stage 4 sleep
Synapse hypothesis: occurs in deeper states of sleep which is why children have more deep sleep than adults
Describe the ascending arousal system
What regulates this pathway and how?
Pathway of neurons intimately involved in controlling sleep/arousal
Lesions in different areas cause sleepiness, insomnia, or narcolepsy
Many neurotransmitters at play here
The ventrolateral preoptic area (VLPO) releases GABA and inhibits any synapses it connects to, including the ascending arousal pathway
Correlation between VLPO activity and being asleep
What are the brain nuclei stimulating wakefulness? What about the brain nucleus inhibiting wakefulness?
Stimulating:
- Locus coeruleus
- Raphe nuclei
- Tuberomammilary nucleus
- Nuclei of the pons-midbrain junction
- Lateral hypothalamus/perifornical region
inhibiting:
- VLPO
Describe the two-process model of sleep control:
Homeostatic process (S): sleep pressure increases with time awake
Circadian process (C): circadian clock controls timing of sleep and wakefulness
Sleep need is the difference between S and C
Graphs: top is normal, bottom is all nighter
You’re more alert during the day after an all-nighter because your C process is telling you to wake up
What are the neuroanatomical, neurochemical and molecular bases of the circadian process (timing of sleep)?
In the night, SCN signals to DMH to signal to VLPO that it’s time to activate -> active VLPO deactivate ascending arousal pathway -> sleepy
DMH also secretes hypocretins which stimulate wakefulness
Hypocretins (aka orexins) are expressed by a discrete set of neurons in the lateral hypothalamus (two hypocretins)
hcrt1 binds hcrtR1 and hcrtR2, hcrt2 binds only hcrtR2 (Stimulates arousal and feeding)
Hypocretins target brain regions involved in regulating sleep and arousal (ascending arousal pathway)
Define narcolepsy and a possible cause of it
What is the flip-flop model of sleep states and how are hypocretins involved?
Excessive daytime sleepiness (sudden sleep attacks), cataplexy, sleep paralysis, hypnagogic hallucinations
Associated with very low hypocretin levels in CSF (degeneration of hypocretin-producing neurons?)
Hypocretin-KO mice go straing from wakefulness to REM sleep (not seen in wt)
Flip flop model: rolling snowball of stimulation/inhibition causes abrupt switch from one sleep state to another
eg LC, TMN, Raphe push for wakefulness, VLPO pushes for sleep
ORX/hypocretins stabilize this balance (stimulate stimulating factors and get inhibited by inhibiting factors)
Without ORX you won’t have the rapid switch, making it easier to flip flop from one state to another
What are the neuroanatomical, neurochemical and molecular bases of the homeostatic process (sleep pressure)?
We don’t know (field is the same as it was 20 years ago)
Adenosine levels increase during waking/sleep deprivation
Caffeine antagonizes adneosine receptor
A2AR KO mice: decreased sleep, decreased response to sleep deprivation
Involves glia (release ATP which is converted to adenosine, increased brain activity during the day leads to buildup of adenosine in neurons during the day)
Candidate gene, Homer 1 a
- RNA levels increase during waking/sleep deprivaiton
- RNA levels go down during sleep
- Known to be involved with synaptic plasticity
Describe the synaptic homeostasis hypothesis
Occurs during slow wave sleep
Pruning of weak synapses and keeping of the strong
