Sleep Flashcards by Imogen Briggs

What are the 6 fundamental behavioral states associated with sleep?

Quiescence, posture, environment retrieval, elevated sensory arousal threshold, reversible, homeostatically regulated

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What two observations define sleep?

Distinct behavior and electrophysiological stages

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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)

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What are the two clues that show there is a function behind sleep?

Universality of sleep across species, sleep deprivation has detrimental effects

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What physiological processes occur during sleep?

Pulsatile release of hormones
Restorative functions
Metabolic clearance of waste
Memory consolidation
Brain development and plasticity

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How does core temperature change during sleep?

It decreases by around one degree celsius

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How does metabolic rate change during sleep?

Decreases by 5-10%

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In which broad stage of sleep does growth hormone secretion increase?

NREM sleep

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How does the rate of CSF flow change during sleep?

It increases - glymphatic system

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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

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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

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Sleep deprivation in middle-aged populations can lead to an increased risk of developing what disorder?

Alzheimer’s disease (Sabia et al, 2021)

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What is meant by the term sleep pressure?

Need and desire to sleep increases as our time awake increases

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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

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Which metabolite is believed to cause sleep pressure via accumulation during waking hours?

Adenosine

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How does adenosine impact sleep pressure?

Increases in concentration during waking hours and increases need to sleep

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How does caffeine promote wakefulness?

Blocks adenosine receptors presynaptically, reduces sleep pressure and increases wakefulness

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Adenosine reduces the release of which three other neurotransmitters?

Acetylcholine
Noradrenaline
Serotonin

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When do adenosine concentrations naturally fall?

During sleep

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Which areas of the brain are involved in forming patterns of sleep/wakefulness?

Suprachiasmatic nucleus in the hypothalamus
Retino-hypothalamic tract

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How does the suprachiasmatic nucleus in the hypothalamus help to regulate circadian rhythms?

Helps to form sleep/wakefulness patterns

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How does light influence sleep patterns?

Depolarizes specialized melanopsin retinal ganglion cells which reduces melatonin secretions and reduces sleepiness

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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

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What is the relationship between light intensity and melatonin secretions?

As light decreases, melatonin secretions increase

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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