Sleep Flashcards
What is sleep
- A readily reversible state of reduced responsiveness to, and interaction with, the environment
What are the functions of sleep
- restorative - cortical recovery, tissue repair- Not a lot of evidence for growth of tissues and cells
- adaptation – protection from nocturnal predators
- metabolism/weight homeostasis
- memory consolidation and integration
How can you record sleep brain activity
- Electroencephalogram - EEG
- Records the activity of populations (many thousands) of neurons
- reveals synchrony of neuronal activity
- Stick electrode on scalp
- Record summed activity of nerves underneath the scalp
- Looks at synchrony of nerves
What does synchronous activity allow
- Synchronous activity gives rise to EEG rhythms
- frequency determines how fast neurones are firing
- amplitude (power) reflects number of neurones in synchrony
What are the different brain rhythms and functional states
- Delta rhythms < 4 Hz
- Theta rhythms – 4-7 Hz
- Alpha rhythms – 8-13 Hz
- Beta rhythms > 14 Hz
- Gamma- higher frequency
Describe state with delta rhythms
- deep dreamless sleep
- synchronized waves
- large amplitude, low frequency
Describe state with theta rhythms
- light sleep, dreaming, mental imagery, meditation, memory
Describe state with alpha rhythms
- conscious relaxation, mental visualisation
Describe state with beta rhythms
- awake, alert, concentration, cognition, motor activity, navigation
Describe state with gamma rhythms
- memory encoding and recall, attention, predictions, cognitive processing
Describe stages of sleep cycle
- Rapid eye movement (REM)
- ~20 min
- Dreaming - Non rapid eye movement (NREM)
- Stages I-4
- 60-90 min
- Repeat cycle 4-6 x - Alternate periods of deep, non-rapid eye movement (non- REM) and REM sleep.
- Each cycle has shorter and shallower non-REM periods and longer REM periods
Describe the rhythms in the sleep cycle
- Awake
- Dominated by alpha and beta rhythms
- high frequency low amplitude - Stage 1-4 Non-REM sleep
- Go towards larger amplitude, low frequency - REM sleep
- Dominated by beta rhythms
Describe changes in REM sleep
- EEG like that of an active waking brain (“paradoxical sleep”)
- Oxygen consumption of brain is high
- Vivid dreaming
- Loss of skeletal muscle tone (atonia)
- Bursts of rapid eye movements
- Sympathetic activity predominates
What else changes in REM sleep
- Sympathetic activity dominates in REM sleep
- REM sleep is accompanied by changes in
- HR,
- respiration,
- local blood flow
Describe changes in NREM sleep
- Non-REM sleep is a rest period
- Muscle tension reduced
- Body temperature lowered
- Energy consumption lowered
- Increase in parasympathetic activity
- Brain rhythms slow (“slow wave sleep”)
What are important areas for control of sleep
- Reticular Activating system
- brain stem lesions result in coma and sleep
- brain stem stimulation induces wakefulness - Thalamic stimulation induces sleep
- Thalamo-cortical inputs control sleep
What system regulates wakefulness and alertness
- Ascending reticular activating system (RAS)- regulate wakefulness and alertness
- RAS– >Thalamus–>cortex
What parts of the brain does the RAS regulate and what neurotransmitter do they effect
- Locus coeruleus – noradenaline
- Raphe nuclei – serotonin
- Brainstem/forebrain – acetylcholine
- Midbrain – histamine
- Increase Firing of these neurons = awakening
- Decrease Firing of these neurons = falling asleep
Describe the ascending Reticular Activating System
- Cholinergic, serotonergic (5HT), noradrenergic neurones in RAS promote increased cortical and thalamic excitation
- Histamine neurones near hypothalamus also contribute excitation
- Orexin neurones in hypothalamus increase activity of RAS and histamine
- RAS/histamine inhibited by GABA/galanin neurones in hypothalamus
What control of onset and offset of REM periods
- by brain stem neurons
- Cholinergic- increases firing as you go into REM
- serotoninergic and noradrenergic neurons increase firing as it goes into NREM
RAS-thalamus-corticol interactions when you are awake
- RAS activates thalamus
- Thalamus generates non-thymic activity
- Cortex entrained into fast waking activity
2) Asleep
RAS-thalamus-corticol interactions when you are asleep
- RAS activity switched off
- Thalamus generates rhythmic activity
- Cortex entrained into low sleep rhythms
List some sleep disorders
- Transient insomnia - noise, shift work, jet lag
- Short term insomnia - emotional issues, stress, anxiety
- Chronic insomnia - pain, depression, alcohol abuse, breathing disorder
- Fatal familial insomnia - rare prion disease
What is a hypnotic
- A drug used to induce and maintain sleep
What should use of hypnotics be
- Intermittent
- short term (< 2 weeks) if daytime impairment is severe
- tolerance may develop
- withdrawal syndromes can occur
- Treatment aims to shorten time to sleep, increase total duration of sleep, without suppressing sleep cycle and REM sleep
What does blue light do
- Supresses production of melatonin
- Pineal gland can’t produce melatonin
- Melatonin can’t regulate your sleep cycle
- Lack of sleep
What are some Benzodiazepine and related hypnotics
- Potentiate GABA inhibition by enhancing GABAA-receptors
- Benzodiazepines
- non-benzodiazepines
- barbiturates and barbiturate-like
Give examples of Benzodiazepines and any problems
- Long acting e.g. nitrazepam, flurazepam
- Short acting e.g. loprazelam, temazepam, flunitrazepam
- problems with tolerance and dependence, and rebound insomnia
Give examples of non-Benzodiazepines and any problems
- zolpidem, zopiclone, zaleplon
- may have sub-unit specificity – potentially less side effects
- different binding site to benzodiazepines
Give examples of barbiturates and barbiturate-like and any problems
- phenobarbitone, methaqualone, meprobamate
2. rarely used now
What are some other potential hypnotics
- Orexin antagonists
- Histamine H1 antagonists or inverse agonists
- Gamma-hydroxybutyrate
- Melatonin receptor agonists
Describe orexin antagonists and give example
- suvorexant
2. orexin is involved in awakening
Describe Histamine H1 antagonists or inverse agonists and give example
- over the counter sleep remedies
2. diphenhydramine, chlorpheniramine
Describe Gamma-hydroxybutyrate and give example
- naturally occurring
2. may be a GABAB-agonist or metabolised to GABA
Give example of Melatonin receptor agonists
- Melatonin (Circadin), ramelton
- may reset disturbed circadian rhythms
- jet lag, shift work patterns
What is narcolepsy
- Pathological increase in sleep
- Sudden onset of sleep episodes and loss of motor control (cataplexy)
- May involve reduced numbers of orexin neurones – loss of RAS activation
What is treatment for narcolepsy
- Stimulant drugs e.g. methylphenidate, modafinil, amphetamine-related
- Antidepressants - SSRIs, SNRIs, TCAs
- Sodium oxybate – (GHB)
- Orexin agonists?
