Sleep

Question 1

What does EEG measure?

Answer 1

Potential differences between two points on the scalps

Question 2

What are the EEG sleep stages in humans?

Answer 2

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)

Question 3

Describe how sleep changes across our lifespan?

Answer 3

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

Question 4

Give examples of diseases that may alter EEG

Answer 4

Schizophrenia (deficits in spindle-activity → increase in REM sleep) ) and neurodegenerative disease

Question 5

Main wake-promoting system

Answer 5

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

Question 6

Aside from the cholinergic system, what other group is known to be wake-promoting? Describe this.

Answer 6

Monoaminergic cell groups that project to the forebrain

1. noradrengic LC
2. Histaminergic neurons in the tuberomammilary nucleus (TMN)
3. Serotoninergic dorsal and median raphe nuclei
4. DA neurons - ventral tegmental area/ substantia nigra pars compacta

Their targets are:

1. lateral hypothalamus
2. brainstem
3. BF
4. cerebral cortex
5. thalamus (mostly intralaminar and reticular nuclei

Question 7

What is the third group of neurons promoting wake?

Answer 7

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)

Question 8

Main wake-promoting system

Answer 8

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

Question 9

Aside from the cholinergic system, what other group is known to be wake-promoting? Describe this.

Answer 9

Monoaminergic cell groups that project to the forebrain

1. noradrengic LC
2. Histaminergic neurons in the tuberomammilary nucleus (TMN)
3. Serotoninergic dorsal and median raphe nuclei
4. DA neurons - ventral tegmental area/ substantia nigra pars compacta

Their targets are:

1. lateral hypothalamus
2. brainstem
3. BF
4. cerebral cortex
5. thalamus (mostly intralaminar and reticular nuclei

Question 10

What is the third group of neurons promoting wake?

Answer 10

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)

Question 11

Overall, what are the key wake promoting ascending pathways

Answer 11

• 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)

Question 12

What substances have been suggested as somnogens?

Answer 12

• 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.

Question 13

Effect of benzos on sleep

Answer 13

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

Question 14

Give examples of benzodiazepines which can induce sleep

Answer 14

Temazepam and diazepam

Question 15

What is the homeostatic drive to sleep from neurons in the preoptic hypothalamic area achieved by?

Answer 15

Inhibition of ascending arousal pathways → via release of inhibitory NTs GABA and galanin

Question 16

Effect of benzos on sleep

Answer 16

They are associated with modest imporvements to sleep latency and longer sleep duration; however, they suppress deep sleep which compromises sleep’s restorative effects

Question 17

Give examples of benzodiazepines which can induce sleep

Answer 17

Temazepam and diazepam

Question 18

Consequences of sleep deprivation

Answer 18

Decrease in vigilance, attention, cognitive functions

Question 19

Describe the circadian clock

Answer 19

Circadian timing in mammals is organized in a hierarchy of multiple circadian oscillators;
• The master clock in the SCN is composed of numerous clock cells. The SCN receives light
information by a direct retinohypothalamic tract (RHT) to entrain the clock to the 24-h day.
• The entrained SCN, in turn, coordinates the timing of oscillators in other brain areas and in
peripheral organs;
• The intracellular clock mechanism involves interacting positive and negative transcriptional
feedback loops that drive recurrent rhythms in the RNA and protein levels of key clock
components

Question 20

describe melatonin with regard to circadian rhythms

Answer 20

• circadian clock drives the release of melatonin from the pineal gland
• it is a biological marker for dark
• it acts on the SCN, forming another feedback loop
• it has been proposed that melaotonin is a chronotherapeutic, helping regularize sleep onset by entraining circadian rhythms

Question 21

Delta waves

Answer 21

Deep sleep

Question 22

Theta waves

Answer 22

Sleeping

Question 23

Alpha waves

Answer 23

Relaxing

Question 24

Beta waves

Answer 24

Awake