Week 6: Sleep

Biorhythms

Circadian

Ultradian

repeating 24 hour cycles

regular 90-120 min cycles of activation and quiet

seen in REM and in brain activity during wakefulness

tied to sleep-wake cycles

Zeitgebers

time givers

Light ☀

entrain internal biological clocks to 24-hour cycle of earth rotation

Free-running circadian rhythms

24.2 to 24.9 hours

occur in absence of light and causes severe sleep disruptions

Relation to Food 🍖

⬆ effective when there is enough food

⬇ effective when there is food shortage

Chronotypes

individual differences in circadian patterns

Lark, night owl, in-between

many switch to owl chronotype in teens

dramatic drop in melatonin on onset of puberty

revert back after puberty possibly due to maturation of sleep regulation brain regions

Disruptions

Shift Maladaptation Syndrome

Jet Lag

Demographic

Symptoms

excessive sleepiness at work,
impaired sleep at home

health, personality, mood and interpersonal problems

affects middle-aged and older workers the most

experienced by individuals working evening or night shifts

affects larks more than night owls

Work impactss

nurses on night shift make 30% more errors

higher accident rates in night shifts

arises from crossing time zones

Symptoms

Irritability 😠

Sleepiness 💤

Chronic Jet Lag

flight attendants that crossed time zones weekly for 4 or more yrs

⬇ Reaction Time

9% more mistakes

Temporal lobe atrophy without sufficient recovery time

easier to adjust to phase-delays than phase-advances

Phase-Delays

travelling West

later shifts than usual

Phase-Advances

travelling East

earlier shifts than usual

Daylight Savings Time

shift clock 1 hour back in fall 🍁 (phase-delay)

shift clock 1 hour forward in spring 🍀 (phase-advance)

produces jet lag symptoms for a few days

associated with cardiovascular disease

sleep deprivation leading to ⬆ SNS activation and
⬆ inflammation

Biology

Superchiasmatic Nucleus

name from its location above (supra) the optic chiasm

receives input from the axons of

Intrinsically photosensitive retinal ganglion cells (ipRGC)

contain a photopigment called melanopsin

forms the retinohypothalamic pathway from the retina to the SCN

Functions

distinguishes between day and night and is most active in day

regardless of activity patterns

cathemeral (☀ and 🌙)

SCN activity generates SNS response

SNS response affects amount of melatonin synthesised by pineal gland

⬇ SNS activity leads to ⬇ melatonin made

⬆ SNS activity leads to ⬆ melatonin made

crepuscular
(active in twilight)

master clock that coordinates peripheral clock activity

maintains circadian rhythms independently

isolated SCN tissue cultures have brain activity fluctuations that match source animal circadian rhythms

Hamsters exhibit cycle length of transplanted SCN

Rat experiments

SCN cells adjust in 1 to 2 cycles

Lung and muscle tissues require 6 cycles

Liver tissues require more than 16 cycles

Astrocytes

most active at 🌙

finely tunes SCN circadian activity

disabling astrocytes leads to slight lengthening of circadian rhythms

Cellular Basis

fruit fly research

Period Gene

Timeless Gene

releases mRNA into the cytoplasm to produce PER proteins

produces TIM proteins

TIMs bind with PERs to form a PER/TIM complex

PER/TIM complex can enter nucleus and inhibit period gene

PER proteins ⬆ at 🌙 and ⬇ in the ☀

Melatonin

released from pineal gland into CSF in the third ventricle

release is suppressed by light

levels increase 2 hours before sleep and drop over the night

Supplementation

helpful in regulating sleep patterns for individuals with visual impairments

has antioxidant properties

can potentially improve symptoms in neurodegenerative disorders such as Alzheimer's

melatonin receptors in cells are involved in immune system

potentially improve immune function

Cortisol

📈 in the morning and 📉 at night

released during stress

stress-induced cortisol associated with poor sleep quality

associated with jet lag effects

flight crew that cross over 8 time zones have 33% more cortisol in saliva than ground crew

Functions

mobilise energy stores

higher heart rate

higher blood pressure

Growth Hormone

Release

Functions

stimulates physical growth in children

building muscle and bone mass

maintaining immune system function

released during Stage 3 of nREM sleep

peaks during puberty onset and drops after 21

reduced by sleep deprivation

EEG Research

Alertness 😮

associated with desynchronous activity (alternating beta and alpha activity)

Beta Waves

Alpha Waves

associated with high alertness and active information processing

rapid waves of 14 to 30 Hz

highly irregular and low amplitude

slightly slower than beta waves with 8 to 13 Hz

more regular and larger amplitude

Mu Waves

frequency overlaps with alpha at 9 to 11 Hz

localised in the motor cortex

advances in EEG may allow researchers to measure gamma-band activity

more than 30 cycles per second

prominent in the front of the brain

prominent in the back of the brain (visual cortex)

observed at rest but suppressed by movement

associated with relaxation

closing eyes can initiate alpha wave activity

obvious during sensory and visual processing

Sleep 😴

Stage 1 NREM

alpha waves replaced by theta wave activity

⬇ in heart rate and muscle tension

Emergence of sleep myoclonia

Stage 2 NREM

Sleep spindles

produced by interactions between the thalamus and cortex

12 to 14 Hz

last around 0.5 seconds

K complexes

made of single delta waves

occur randomly or in response to unexpected stimuli (eg. loud noises)

accounts for 50% of sleep

Stage 3 NREM

features delta wave activity (1 to 4 Hz)

Brain energy usage decreases to 11% to 40% of waking brain

PNS activity lowers blood pressure, heart rate, breathing, body temperature

Sharp-wave ripples

occur in the hippocampus

rapid bursts of waveforms

REM

vivid dreaming

features waking beta activity and theta activity in the hippocampus

brain energy usage increases to or beyond wakefulness levels

SNS activation

increase in blood pressure, breathing and heart rate

increased blood flow in genital areas

major postural muscles are immobilised while smaller muscles can still twitch

Patterns

1st 4 hours

longer periods of NREM and short REM periods

Stage 3 NREM is dominant

Next 4 hours

REM is dominant stage

Any NREM will be in Stages 1 to 2

Stage 3 NREM infrequent or absent

behaviours that occur at regular intervals in response to internal, biological clocks

Networks

Waking

Ventral Pathway

Dorsal Pathway

Medulla ➡ Hypothalamus ➡ basal forebrain

Cholinergic
mesopontine nuclei

found in midbrain reticular formation

secrete acetylcholine

found in junction of the pons (pontine) and midbrain (meso)

Locus Coeruleus

Anterior Raphe Nuclei

important in managing sleep-wake cycles

communicates with preoptic area, SCN and cerebral cortex

secretes most of the brain's norepinephrine

has connections to the thalamus, hippocampus and cortex

communicates with thalamus which moderates cerebral cortex activity and amount of sensory input received

⬆ activity with alertness

⬆ activity with alertness

Default Mode Network

consists of the medial prefrontal, medial parietal, lateral parietal, lateral temporal

Functions

mind wandering

recalling personally relevant memories

planning future events

thinking about beliefs, intentions and motivations of others

overlap of DMN structures with those involved in social behaviour

DMN connectivity

useful predictor of cognitive function

peaks in adulthood and is lower in childhood and older age

unusual DMN activity implicated in neurodegenerative and psychological disorders

Sharing or understanding personal stories and experiencing fictional situations

Integrating internal thoughts and external stimuli to establish a context for understanding situations

NREM Sleep

Preoptic Area (POA)

Functions

aka NREM-on cells

stimulation ⚡ of POA cells produces immediate NREM sleep

lesions result in insomnia

⬇ activity during waking and REM

manage homeostatic control of wakefulness

inhibits waking pathways

Thalamus

synchronises cortical neuron activity in absence of waking circuit activity

electrical stimulation in waking animals produces NREM sleep

DMN

decoupling of anterior parts from posterior parts

possibly associated with reduced consciousness during deep sleep

REM Sleep

CMN

high levels of activity during REM and waking

electrical stimulation produces desynchronous activity

due to connections with thalamus and cortex

REM-on

Rostral Pontine Reticular Formation

found in the pons

lesions in the area inhibit REM sleep

active during REM while inactive in waking and REM

REM-off

Locus Coeruleus

Raphe Nuclei

reduction in REM-off area activity permits REM-on area activity

allows REM to occur

REM-off areas reactivate after 30min of REM, inhibiting REM-on areas

PGO waves

1⃣ PRF stimulates superior colliculi, which communicates with different area of PRF

Responsible for coordinating eye movement timing and direction

2⃣ Lateral Geniculate nucleus is activated

visual centre of the thalamus

3⃣ Occipital lobe
is activated

visual experiences are triggered

location of the primary visual cortex

Muscular Paralysis

Inhibitory signals from PRF ➡ medulla ➡ spinal cord motor systems

rapid eye movements

only occur during 14%-27% of REM

experienced by people with congenital blindness

fingers twitching indicates muscular inhibition stronger at beginning of REM and gradually decreases

Others

⬆ activity in

V2 (secondary visual cortex)

Hippocampus

⬇ activity in

Limbic System

frontal lobe

parietal lobe

DMN

suggests REM significance in memory consolidation

underlie emotional content of dreams

possible reason for illogical nature of dreams

basis for self-referential aspect of dreams

lower DMN activity associated with rapid eye movements

associated with rapid eye movements

Biological Correlates

Alertness

Glutamate

Acetylcholine

⬆ in waking and REM sleep but ⬇ in NREM sleep

⬆ in waking and REM sleep but ⬇ in NREM sleep

Histamines

major neurochemical used by neurons in the thalamus and the hypothalamus

⬆ activity in waking and ⬇ in NREM and REM sleep

neuron activity associated with alertness

Antihistamines

Traditional ones produce drowsiness 😪

Modern ones do not cross blood-brain barrier and do not induce drowsiness

Caffeine ☕

blocks adenosine receptors

REM-off areas

Norepinephrine produced by locus coeruleus

Serotonin produced by raphe nuclei

antidepressant drugs boost both and thus suppress REM

Highest in wakefulness and lowest in REM

promotes alertness

Drowsiness

Adenosine

⬆ throughout the day and until sleep occurs and ⬇ during sleep

prevents secretion of neurochemicals associated with waking

eg. ACh, norepinephrine, serotonin

released by pons and basal forebrain

ATP byproduct that inhibits many brain systems

cholinergic agonists ⬆ mental awareness

Eg. nicotine 🚬

possibly promotes REM-on processes