Sleep

Question 1

What is sleep

Answer 1

1. A readily reversible state of reduced responsiveness to, and interaction with, the environment

Question 2

What are the functions of sleep

Answer 2

1. restorative - cortical recovery, tissue repair- Not a lot of evidence for growth of tissues and cells
2. adaptation – protection from nocturnal predators
3. metabolism/weight homeostasis
4. memory consolidation and integration

Question 3

How can you record sleep brain activity

Answer 3

1. Electroencephalogram - EEG
2. Records the activity of populations (many thousands) of neurons
3. reveals synchrony of neuronal activity
4. Stick electrode on scalp
5. Record summed activity of nerves underneath the scalp
6. Looks at synchrony of nerves

Question 4

What does synchronous activity allow

Answer 4

1. Synchronous activity gives rise to EEG rhythms
2. frequency determines how fast neurones are firing
3. amplitude (power) reflects number of neurones in synchrony

Question 5

What are the different brain rhythms and functional states

Answer 5

1. Delta rhythms < 4 Hz
2. Theta rhythms – 4-7 Hz
3. Alpha rhythms – 8-13 Hz
4. Beta rhythms > 14 Hz
5. Gamma- higher frequency

Question 6

Describe state with delta rhythms

Answer 6

1. deep dreamless sleep
2. synchronized waves
3. large amplitude, low frequency

Question 7

Describe state with theta rhythms

Answer 7

1. light sleep, dreaming, mental imagery, meditation, memory

Question 8

Describe state with alpha rhythms

Answer 8

1. conscious relaxation, mental visualisation

Question 9

Describe state with beta rhythms

Answer 9

1. awake, alert, concentration, cognition, motor activity, navigation

Question 10

Describe state with gamma rhythms

Answer 10

1. memory encoding and recall, attention, predictions, cognitive processing

Question 11

Describe stages of sleep cycle

Answer 11

1. Rapid eye movement (REM)
   - ~20 min
   - Dreaming
2. Non rapid eye movement (NREM)
   - Stages I-4
   - 60-90 min
   - Repeat cycle 4-6 x
3. Alternate periods of deep, non-rapid eye movement (non- REM) and REM sleep.
4. Each cycle has shorter and shallower non-REM periods and longer REM periods

Question 12

Describe the rhythms in the sleep cycle

Answer 12

1. Awake
   - Dominated by alpha and beta rhythms
   - high frequency low amplitude
2. Stage 1-4 Non-REM sleep
   - Go towards larger amplitude, low frequency
3. REM sleep
   - Dominated by beta rhythms

Question 13

Describe changes in REM sleep

Answer 13

1. EEG like that of an active waking brain (“paradoxical sleep”)
2. Oxygen consumption of brain is high
3. Vivid dreaming
4. Loss of skeletal muscle tone (atonia)
5. Bursts of rapid eye movements
6. Sympathetic activity predominates

Question 14

What else changes in REM sleep

Answer 14

1. Sympathetic activity dominates in REM sleep
2. REM sleep is accompanied by changes in
3. HR,
4. respiration,
5. local blood flow

Question 15

Describe changes in NREM sleep

Answer 15

1. Non-REM sleep is a rest period
2. Muscle tension reduced
3. Body temperature lowered
4. Energy consumption lowered
5. Increase in parasympathetic activity
6. Brain rhythms slow (“slow wave sleep”)

Question 16

What are important areas for control of sleep

Answer 16

1. Reticular Activating system
   - brain stem lesions result in coma and sleep
   - brain stem stimulation induces wakefulness
2. Thalamic stimulation induces sleep
3. Thalamo-cortical inputs control sleep

Question 17

What system regulates wakefulness and alertness

Answer 17

1. Ascending reticular activating system (RAS)- regulate wakefulness and alertness
2. RAS– >Thalamus–>cortex

Question 18

What parts of the brain does the RAS regulate and what neurotransmitter do they effect

Answer 18

1. Locus coeruleus – noradenaline
2. Raphe nuclei – serotonin
3. Brainstem/forebrain – acetylcholine
4. Midbrain – histamine
5. Increase Firing of these neurons = awakening
6. Decrease Firing of these neurons = falling asleep

Question 19

Describe the ascending Reticular Activating System

Answer 19

1. Cholinergic, serotonergic (5HT), noradrenergic neurones in RAS promote increased cortical and thalamic excitation
2. Histamine neurones near hypothalamus also contribute excitation
3. Orexin neurones in hypothalamus increase activity of RAS and histamine
4. RAS/histamine inhibited by GABA/galanin neurones in hypothalamus

Question 20

What control of onset and offset of REM periods

Answer 20

1. by brain stem neurons
2. Cholinergic- increases firing as you go into REM
3. serotoninergic and noradrenergic neurons increase firing as it goes into NREM

Question 21

RAS-thalamus-corticol interactions when you are awake

Answer 21

1. RAS activates thalamus
2. Thalamus generates non-thymic activity
3. Cortex entrained into fast waking activity
   2) Asleep

Question 22

RAS-thalamus-corticol interactions when you are asleep

Answer 22

1. RAS activity switched off
2. Thalamus generates rhythmic activity
3. Cortex entrained into low sleep rhythms

Question 23

List some sleep disorders

Answer 23

1. Transient insomnia - noise, shift work, jet lag
2. Short term insomnia - emotional issues, stress, anxiety
3. Chronic insomnia - pain, depression, alcohol abuse, breathing disorder
4. Fatal familial insomnia - rare prion disease

Question 24

What is a hypnotic

Answer 24

1. A drug used to induce and maintain sleep

Question 25

What should use of hypnotics be

Answer 25

1. Intermittent 2. short term (< 2 weeks) if daytime impairment is severe 3. tolerance may develop 4. withdrawal syndromes can occur 5. Treatment aims to shorten time to sleep, increase total duration of sleep, without suppressing sleep cycle and REM sleep

Question 26

What does blue light do

Answer 26

1. Supresses production of melatonin 2. Pineal gland can’t produce melatonin 3. Melatonin can’t regulate your sleep cycle 4. Lack of sleep

Question 27

What are some Benzodiazepine and related hypnotics

Answer 27

1. Potentiate GABA inhibition by enhancing GABAA-receptors 2. Benzodiazepines 3. non-benzodiazepines 4. barbiturates and barbiturate-like

Question 28

Give examples of Benzodiazepines and any problems

Answer 28

1. Long acting e.g. nitrazepam, flurazepam 2. Short acting e.g. loprazelam, temazepam, flunitrazepam 3. problems with tolerance and dependence, and rebound insomnia

Question 29

Give examples of non-Benzodiazepines and any problems

Answer 29

1. zolpidem, zopiclone, zaleplon 2. may have sub-unit specificity – potentially less side effects 3. different binding site to benzodiazepines

Question 30

Give examples of barbiturates and barbiturate-like and any problems

Answer 30

1. phenobarbitone, methaqualone, meprobamate | 2. rarely used now

Question 31

What are some other potential hypnotics

Answer 31

1. Orexin antagonists 2. Histamine H1 antagonists or inverse agonists 3. Gamma-hydroxybutyrate 4. Melatonin receptor agonists

Question 32

Describe orexin antagonists and give example

Answer 32

1. suvorexant | 2. orexin is involved in awakening

Question 33

Describe Histamine H1 antagonists or inverse agonists and give example

Answer 33

1. over the counter sleep remedies | 2. diphenhydramine, chlorpheniramine

Question 34

Describe Gamma-hydroxybutyrate and give example

Answer 34

1. naturally occurring | 2. may be a GABAB-agonist or metabolised to GABA

Question 35

Give example of Melatonin receptor agonists

Answer 35

1. Melatonin (Circadin), ramelton 2. may reset disturbed circadian rhythms 3. jet lag, shift work patterns

Question 36

What is narcolepsy

Answer 36

1. Pathological increase in sleep 2. Sudden onset of sleep episodes and loss of motor control (cataplexy) 3. May involve reduced numbers of orexin neurones – loss of RAS activation

Question 37

What is treatment for narcolepsy

Answer 37

1. Stimulant drugs e.g. methylphenidate, modafinil, amphetamine-related 2. Antidepressants - SSRIs, SNRIs, TCAs 3. Sodium oxybate – (GHB) 4. Orexin agonists?