Sleep Flashcards
What are the 6 fundamental behavioral states associated with sleep?
Quiescence, posture, environment retrieval, elevated sensory arousal threshold, reversible, homeostatically regulated
What two observations define sleep?
Distinct behavior and electrophysiological stages
What do the leading theories point to for the function behind why we sleep?
Supports the CNS via maintenance/recovery (removal of waste) and computational power (regulating strength of synaptic connections)
What are the two clues that show there is a function behind sleep?
Universality of sleep across species, sleep deprivation has detrimental effects
What physiological processes occur during sleep?
Pulsatile release of hormones
Restorative functions
Metabolic clearance of waste
Memory consolidation
Brain development and plasticity
How does core temperature change during sleep?
It decreases by around one degree celsius
How does metabolic rate change during sleep?
Decreases by 5-10%
In which broad stage of sleep does growth hormone secretion increase?
NREM sleep
How does the rate of CSF flow change during sleep?
It increases - glymphatic system
What consequences does sleep deprivation have on the body?
Delirium
Mood changes
Lack of concentration
Loss of memory
Confusion
Paranoia
Hallucinations
ROS build up in gut
It is fatal - increases risk of illness and death
What did the Stanford sleep deprivation experiment involving Randy Gardner reveal about the brain’s protective measures during sleep deprivation?
The brain takes ‘micronaps’ of a few seconds long. Whilst the person is still awake, parts of the brain sleep
Sleep deprivation in middle-aged populations can lead to an increased risk of developing what disorder?
Alzheimer’s disease (Sabia et al, 2021)
What is meant by the term sleep pressure?
Need and desire to sleep increases as our time awake increases
Following sleep deprivation, what differences do the first and subsequent nights show in regards to sleep patterns?
First night: longer slow wave NREM sleep
Subsequent nights: longer REM sleep
Which metabolite is believed to cause sleep pressure via accumulation during waking hours?
Adenosine
How does adenosine impact sleep pressure?
Increases in concentration during waking hours and increases need to sleep
How does caffeine promote wakefulness?
Blocks adenosine receptors presynaptically, reduces sleep pressure and increases wakefulness
Adenosine reduces the release of which three other neurotransmitters?
Acetylcholine
Noradrenaline
Serotonin
When do adenosine concentrations naturally fall?
During sleep
Which areas of the brain are involved in forming patterns of sleep/wakefulness?
Suprachiasmatic nucleus in the hypothalamus
Retino-hypothalamic tract
How does the suprachiasmatic nucleus in the hypothalamus help to regulate circadian rhythms?
Helps to form sleep/wakefulness patterns
How does light influence sleep patterns?
Depolarizes specialized melanopsin retinal ganglion cells which reduces melatonin secretions and reduces sleepiness
What is the pathway of how retinal ganglion cells induce melatonin secretion?
Retinal ganglion cells > suprachiasmatic nucleus (hypothalamus) > paraventricular nucleus (hypothalamus) > superior cervical ganglion > pineal gland > melatonin
Retinal ganglion cells activate the suprachiasmatic nucleus which projects to the paraventricular nucleus of the hypothalamus. This relays a message to the superior cervical ganglion which projects to the pineal gland and induces melatonin secretion
What is the relationship between light intensity and melatonin secretions?
As light decreases, melatonin secretions increase
How does the hypothalamus contribute to the neural control of sleep?
Suprachiasmatic nucleus regulates circadian rhythms
How does the brain stem contribute to the neural control of sleep?
Reticular activating system is involved in arousal and wakefulness
What is the reticular activation system?
Network of neurons in brain stem involved in arousal and wakefulness
What type of neurons innervate the reticular activation system?
Cholinergic neurons
How does the thalamus contribute to the neural control of sleep?
Thalamocortical pathways generate spindles during NREM sleep - hallmark sign of stage 2 NREM
Sleep requires interaction between which 4 structures in the brain?
Thalamus
Hypothalamus
Cortex
Brain stem
What are sleep spindles?
Oscillation pattern generated by thalamic reticular nucleus (and other thalamic nuclei) during stage 2 NREM sleep
What are K complexes and what induces them?
EEG pattern of sudden high amplitude sharp wave that can either be induced by sudden external sensory stimuli (a loud noise for example) or can be generated spontaneously
During which stage of sleep are K complexes and spindles observed on EEG?
Stage 2 NREM
What waves are viewed on EEG during an awake period?
Alpha waves of 8-12Hz
What waves are viewed on EEG during stage 1 NREM sleep?
Mixed lower frequency waves that have a higher amplitude, alpha and theta waves
What waves are viewed on EEG during stage 2 NREM sleep?
Lower frequency sinusoidal waves, spindles and K complexes present
What age do spindles start to occur during sleep?
Infancy - 4 to 9 weeks post birth
What age do K complexes start to occur during sleep?
Infancy - 5 to 6 months
At what stage in development/life do K complexes start to decrease in amplitude and spindles start to decrease in density?
Over 50 years of age
What waves are seen on EEG during stage 3 NREM sleep?
Beginnings of slow delta wave activity with large amplitude, frequency around 2Hz
What waves are seen on EEG during stage 4 NREM sleep?
Large delta wave rhythms are seen of 2Hz or less
Which stage of sleep is the deepest?
Stage 4 NREM
What waves are seen during REM sleep on EEG?
Low amplitude and mixed frequency waves
EEG patterns observed during REM sleep are indistinguishable from an EEG from which stage of sleep?
Arousal/awake
What physiological process occurs during REM sleep?
Atonia - paralysis of muscles except for eyes
What changes occur to oxygen consumption in the brain during REM sleep?
Oxygen consumption is higher during REM sleep than awake
How does the brain cycle through the stages of sleep?
Repeated cycles of NREM and REM sleep with occasional awake periods. Periods of NREM reduce throughout the night whilst REM periods increase throughout the night.
How does age influence sleep patterns?
Older age is associated with more frequent and prolonged awakenings in the night
Are thalamocortical neurons activated or inhibited during sleep?
Thalamocortical neurons are tonically activated during sleep
Which system/network of neurons activates thalamocortical neurons during sleep?
Reticular activating system activates thalamocortical neurons during sleep
What allows thalamocortical neurons to be rhythmic in their oscillations?
Low threshold voltage gated calcium channels
What do low threshold voltage gated calcium channels allow thalamocortical neurons to do?
Generate rhythmic self-sustaining patterns without external input - when they are sufficiently hyperpolarised
What type of feedback allows for the synchrony to be created between thalamic neurons?
Collective feedback from excitatory and inhibitory synaptic connections
How do synchronous thalamic rhythms pass the rhythm to the cortex?
Thalamocortical axons innervate the cortex and excite cortical extrapyramidal neurons
How are sleep spindles formed?
Recurrent inhibitory and excitatory signals between thalamic excitatory and inhibitory neurons and cortical neurons during stage 2 NREM sleep
Where are memories encoded for short term storage?
Memories are stored short term in the hippocampus
Where are memories encoded for long term storage?
Neocortex
How are memories consolidated from short term to long term storage?
Repeated activation of top-down neocortical slow oscillations in the hippocampus causes an event called triple coupling of oscillations. This causes the memories to be redistributed to the neocortex
In which stage of sleep are memories consolidated from short to long term storage?
NREM sleep
Which stage of sleep is categorized by atonia?
REM sleep
What is the neural basis of atonia in REM sleep?
GABAergic neurons in the pons are activated which inhibit dorsal column neurons. Decreased perception of sensory stimuli occurs.
Inhibitory noradrenergic and serotonergic neurons are inhibited. Cholinergic neurons in the pons are disinhibited.
Glutamatergic neurons are activated. Glycinergic inhibitory neurons in the spinal cord activated.
Motor neurons are inhibited - no muscle movement (atonia)
How can sleep be pharmacologically modulated?
By stimulants (promoting arousal) or sleep promoters
How do amphetamines influence sleep through neurotransmitters?
Inhibit reuptake of dopamine and noradrenaline, resulting in increased wakefulness and arousal
What are examples of amphetamines?
Methylphenidate (Ritalin) and modafinil (Provigil)
When is the use of amphetamines contraindicated?
Hypertension
History of tic disorder
History of depression or bipolar disorder
Recent use of monoamine oxidase inhibitors
History of addiction
How does caffeine impact sleep?
Blocks adenosine receptors and increases dopamine release resulting in increased arousal
How do antihistamines influence sleep?
Promote sleep by blocking effects of histamine. Histamine activates cortical neurons involved in arousal. Therefore, must cross BBB
What is an example of an antihistamine that promotes sleep?
Diphenhydramine (Benadryl)
How do GABA agonists influence sleep?
Promote sleep
What are examples of GABA agonists that promote sleep?
Benzodiazepines such as diazepam (Valium)
Gaboxadol
Propofol
Zolpidem (Ambien)
What is narcolepsy?
It is a chronic sleep disorder in which the brain struggles to regulate sleep-wake cycles
What symptoms are associated with narcolepsy?
Excessive day-time tiredness, cataplexy, sleep paralysis, and rapid REM onset
What physiological differences have been observed in the neuronal populations of narcoleptic patients?
Fewer orexin neurons, potentially due to autoimmune destruction
What role do orexin neurons have in the healthy individual?
Active during arousal
What potential pharmacological development shows promise as a treatment for narcolepsy?
Orexin agonists
What is fatal familial insomnia?
An extremely rare, fatal, inherited prion disease caused by a mutation on the PrnP gene that causes a misfolded protein PrP - a prion
How many people around the world have fatal familial insomnia?
40 families worldwide
What inheritance pattern causes fatal familial insomnia?
Autosomal dominant
Which gene is mutated in fatal familial insomnia?
PrnP gene
Which protein is misfolded to create a prion in fatal familial insomnia?
PrP
Which area of the brain is damaged in fatal familial insomnia?
Thalamus
How is the thalamus damaged in fatal familial insomnia?
Accumulation of PrP prion
What are the symptoms associated with fatal familial insomnia?
Progressive insomnia
Significant physical and metal deterioration
Dementia
Eventual death
What is the prognosis of fatal familial insomnia?
Death occurs within 6 months, on average
What is the typical age of onset for fatal familial insomnia?
Middle aged
