Sleep Flashcards
What does EEG measure?
Potential differences between two points on the scalps
What are the EEG sleep stages in humans?
Wakefulness
NREM stage 1 → if you wake up from this you would usually deny being asleep
NREM stage 2 → Predominant stage - we spend most of our sleep in this → It has two major types of oscillation - sleep spindle and K complex
NREM stage 3 → High amplitude slow waves
Thought to be the deepest stage
REM sleep → During phasic REM sleep, eye movements are especially frequent and arousal threshold might be quite high (hard to wake up the subject)
Describe how sleep changes across our lifespan?
E.g. in very young children, most sleep is REM or active sleep, in teenagers, slow wave activity may have much higher amplitude than in adulthood
Give examples of diseases that may alter EEG
Schizophrenia (deficits in spindle-activity → increase in REM sleep) ) and neurodegenerative disease
Main wake-promoting system
Cholinergic system
- Pedunculopontine/laterodorsal tegmental nuclei project to basal forebrain → BF projects widely to cortex
- ACh = increases the excitability of cortical pyramidal cells and promotes tonic firing by closing K+ channels through mAChRs
Aside from the cholinergic system, what other group is known to be wake-promoting? Describe this.
Monoaminergic cell groups that project to the forebrain
- noradrengic LC
- Histaminergic neurons in the tuberomammilary nucleus (TMN)
- Serotoninergic dorsal and median raphe nuclei
- DA neurons - ventral tegmental area/ substantia nigra pars compacta
Their targets are:
- lateral hypothalamus
- brainstem
- BF
- cerebral cortex
- thalamus (mostly intralaminar and reticular nuclei
What is the third group of neurons promoting wake?
Orexin/hypocretin
Orexin = synthesized in and released from the lateral hypothalamus
They go to the entire cortex, brainstem, BF (particularly intense input to TMN and LC)
Main wake-promoting system
Cholinergic system
- Pedunculopontine/laterodorsal tegmental nuclei project to basal forebrain → BF projects widely to cortex
- ACh = increases the excitability of cortical pyramidal cells and promotes tonic firing by closing K+ channels through mAChRs
Aside from the cholinergic system, what other group is known to be wake-promoting? Describe this.
Monoaminergic cell groups that project to the forebrain
- noradrengic LC
- Histaminergic neurons in the tuberomammilary nucleus (TMN)
- Serotoninergic dorsal and median raphe nuclei
- DA neurons - ventral tegmental area/ substantia nigra pars compacta
Their targets are:
- lateral hypothalamus
- brainstem
- BF
- cerebral cortex
- thalamus (mostly intralaminar and reticular nuclei
What is the third group of neurons promoting wake?
Orexin/hypocretin
Orexin = synthesized in and released from the lateral hypothalamus
They go to the entire cortex, brainstem, BF (particularly intense input to TMN and LC)
Overall, what are the key wake promoting ascending pathways
- cholinergic (from the laterodorsal and pedunculopontine tegmental nuclei, LDT/PPT)
- noradrenergic (from the locus coeruleus, LC)
- serotonergic (from the dorsal and median raphe nuclei)
- dopaminergic (from the ventrolateral tegmental area, VTA)
- glutamatergic (from the parabrachial nucleus, PB)
- histaminergic (from the tuberomammillary nucleus, TMN)
What substances have been suggested as somnogens?
- Adenosine (AD), prostaglandin D2, and cytokines (e.g. interleukin-1 and TNF-α) have all been implicated as somnogens, but there is most evidence for AD as a sleep driver.
- Moreover, AD receptor antagonists, including caffeine and theophylline, are widely used as CNS stimulants to induce vigilance and increase the time spent awake.
- During prolonged wakefulness, brain glycogen is exhausted and ATP levels become depleted. So during these periods, as ATP is degraded to ADP, AMP and eventually AD, and extracellular AD levels rise in some parts of the brain, including the BF.
- This leads us to hypothesise that the sleepiness and sleep-promoting effects of AD are both mediated by adenosinergic inhibition of a cortically projecting BF arousal system.
Effect of benzos on sleep
They are associated with modest imporvements to sleep latency and longer sleep duration; however, they suppress deep sleep which compromises sleep’s restorative effects
GABA agonists
Give examples of benzodiazepines which can induce sleep
Temazepam and diazepam
What is the homeostatic drive to sleep from neurons in the preoptic hypothalamic area achieved by?
Inhibition of ascending arousal pathways → via release of inhibitory NTs GABA and galanin
