MEDS2012 Module 3 - Sleep and Circadian Rhythms

Effects of sleep

- decreased muscle activity

- naturall recurring

- decreased consciousness + responsiveness

- reversible physiological state

- altered brain activity

Outline the 4 stages of the sleep cycle

N1, N2, N3, REM

Outline N1 stage

- 5% of sleep cycle

- decreased brain activity

- lightest sleep

- memory consolidation

Outline N2 stage

- 50%

- decreased temp.

- decreased muscle activity

- decreased breathing

Outline N3 stage

- 25%

- deepest sleep

- memory

- repair

- immunity

Outline REM

- 25%

- Increased brain activity

- memory and learning

- dreaming

- muscle atonia

What is melatonin

sleep hormone

what is serotonin

sleep and arousal

dopamine

emotional processing

acetylcholine

memory consolidation

GABA

restful, restorative sleep

Histmanine

arousal

cortisol

stress, arousal

epinephrine

arousal

Outline the role of the HYPOTHALAMUS regarding arousal from sleep

releases Orexin and histamine --> arousal

Outline the role of the BASAL FOREBRAIN regarding arousal from sleep

releases ACh --> cortical activation

Outline the role of the SCN regarding arousal from sleep

receives signals from retina

signals to pineal gland to stop releasing melatonin

Outline the role of the VLPO regarding arousal from sleep

inhibited by decreasing adenosine and ACh, serotonin, and norepinephrine from brainstem --> arousal

Outline the role of the PONS regarding arousal from sleep

neurons produce ACh exciting Thalamus

Outline the role of the RETICULAR FORMATION regarding arousal from sleep

serotonin, dopamine, norepenephrine. --> cortical activation

Outline the role of the ADRENAL GLAND regarding arousal from sleep

cortisol and norepenephrine --> arousal

Outline the role of the THALAMUS regarding arousal from sleep

increases sensory relay to cortex, and consciousness

Outline the role of the CEREBRAL CORTEX regarding arousal from sleep

receives increased sensory relay from thalamus --> consciousness

Outline the role of the HYPOTHALAMUS regarding sleep onset

contains SCN and VLPO

Outline the role of the BASAL FOREBRAIN regarding sleep onset

releases GABA inhibiting brainstem nuclei --> sleep

Outline the role of the SCN regarding sleep onset

receives signals from retina

signals to pineal gland to release melatonin

Outline the role of the VLPO regarding sleep onset

activated by adenosine

releases GABA inhibiting arousal centres

Outline the role of the PONS regarding sleep onset

signals to hypothalamus --> REM

Outline the role of the AMYGDALA AND HIPPO. regarding sleep onset

memory and dreaming

Outline the role of the RETICULAR FORMATION regarding sleep onset

inhibited by GABA from the VLPO and basal forebrain

Outline the role of the THALAMUS regarding sleep onset

decreases sensory relay to cortex --> sleep

Outline the role of the PINEAL GLAND regarding sleep onset

releasing melatonin --> sleep

Outline the role of the CEREBRAL CORTEX regarding sleep onset

receives reduced sensory relay from hypothalamus, reducing consciousness

memory and learning in NREM sleep

strengthening of declarative memories. hippocampus and cortex

memory and learning in REM sleep

consolidation of emotional memories and learned procedural tasks. amygdala and cortex

repair and detoxification in NREM sleep

- glymphatic system clears metabolic waste via CSF and lympatic system, e.g., amyloid beta proteins

- GH promotes tissues repair, muscle and bone growth, and cell regeneration

immune function in NREM sleep

- increase in GH levels to support immune cell proliferation/repair

- cytokines released to fight infections, inflammation

- support of T-cell memory and antibody function

How do sleep, eating, and breathing interact normally?

Sleep, gut microbes, and breathing regulate each other: healthy microbiota support sleep hormones; normal breathing supports NREM/REM; low inflammation keeps all three stable.

What happens when sleep is disrupted?

↓ serotonin/melatonin, ↑ cortisol & cytokines → gut dysbiosis, inflammation, impaired breathing, and fragmented sleep.

What are the measurements of sleep?

EEG

EOG

EMG

ECG

Outline EEG

spontaneous electrical activity of cortical neurons neurons

--> sleep stages

Outline EOG

eye movements

--> REM

Outline EMG

muscle activity (chin)

--> sleep-related movement disorders

Outline ECG

heart rhythm --> sleep disorders (apnea)

What is sleep pressure?

Circadian drive for wake vs homeostatic drive for sleep

consequences of sleep deprivation

- weakened immune system

- cognitive impairment

- hormone imbalance

- low energy levels

- mood swings and irritability

- increased risk of chronic diseases/obesity/accidents

Outline the sleep changes across the lifespan

- decreased sleep with age (brain development)

infants --> shorter sleep cycles, more REM

Circadian clock

SCN-driven 24-hour rhythm regulating sleep, hormones, and behaviour.

Light entrainment

Light → retinal ganglion cells → SCN → melatonin suppressed → circadian clock shifted.

Phase response curve

Morning light advances the clock; evening/night light delays the clock.

Eastward travel light strategy

Need phase advance → seek morning light, avoid evening light.

Westward travel light strategy

Need phase delay → seek evening light, avoid morning light.

Circadian desynchrony

Internal clock out of sync with environment → sleep, mood, metabolic disruption.

Social jetlag

Difference between biological clock and social schedule → associated with poor sleep and health risks.

Social jetlag across lifespan

Highest in adolescence; declines with age.

How are the SCN and peripheral clocks synchronised?

Light, activity, meals and temperature

How do rhythms feed back?

They regulate clock function via hormonal + neuronal signalling.

Effect of single exercise bout on circadian phase

Night: delays phase; Morning: advances phase.

When is exercise most beneficial for cardiovascular health?

Midday-afternoon exercise.

What intensity improves metabolic outcomes?

Moderate (50-70% max HR).

Exercise effects on sleep

↑ sleep quantity, ↑ SWS, ↓ sleep latency.

What intensity improves sleep best?

Moderate > vigorous.

How does night-eating affect rhythms?

Disrupts hormonal + neurotransmitter rhythms → metabolic dysregulation.

What system is strongly controlled by circadian rhythms?

The GI system (motility, enzymes, antioxidants).

How does misaligned feeding impair metabolism?

Alters clock-gene expression → metabolic impairment.

Mediterranean diet effect on sleep

Improved sleep, ↓ inflammation, neuroprotection via omega-3.

Key nutrient for melatonin synthesis

Tryptophan.

Moderate exercise at night causes

Phase delay.

What is SUDI?

Umbrella term for all sudden unexpected deaths <1 year.

What is SIDS?

Sudden unexplained death in infant <1 year with no cause after complete investigation.

Peak incidence of SIDS

2-4 months.

Season with highest incidence

Winter.

Why are males at higher risk?

Male infants show greater vulnerability (consistent but unclear why).

Non-modifiable SIDS risk factors

Male sex, prematurity, low birth weight, prenatal smoke/drug exposure, infection, genetics.

Modifiable SIDS risk factors

Prone sleeping, co-sleeping, soft bedding, overheating, parental smoking.

Triple-risk model components

Vulnerable infant + critical developmental period + external stressor.

Physiological abnormalities in SIDS

Impaired gas exchange, poor arousal, unstable heart rate.

Key brainstem abnormality

Abnormal serotonin (5-HT) receptor binding/function.

Neurotransmitter abnormalities

Altered ACh and GABAergic signalling.

Key inflammatory findings

Elevated IL-6 and IL-10 in CSF.

Role of BDNF

Growth factor abnormalities impair arousal and respiratory regulation.

Important genetic polymorphism

Long QT syndrome polymorphisms ↑ risk of fatal arrhythmia.

Common prodromal symptoms before SIDS

Mild respiratory infection days-weeks before death.

Cause of HAT

Trypanosoma brucei infection.

Vector

Tsetse fly.

Two subspecies

T. b. gambiense (chronic) & T. b. rhodesiense (acute).

Course of T. b. rhodesiense

Acute febrile illness → CNS invasion → death in months.

Course of T. b. gambiense

Slow, progressive illness over ~3 years.

Why "sleeping sickness"?

Profound sleep/wake disruption, altered temperature + endocrine rhythms.

Main question about symptoms

Are changes due to illness/fatigue or true circadian disruption?

Effect on locomotor activity

Infected mice show reduced wheel-running.

Effect on circadian sleep/feeding

Disrupted feeding, fragmented sleep, shortened circadian period.

Key circadian timing effect

Phase advance during rest phase.

Does Plasmodium infection alter circadian period?

No, period remains unchanged.

What shortens circadian period?

Direct presence of T. brucei parasites, not immune response.

Overall conclusion

T. brucei directly disrupts host circadian machinery at organism, tissue, and cellular levels.

Sedation (definition)

Reduction in excitement, vigilance, and physiological arousal.

Hypnosis (definition)

Drug-induced ability to cause drowsiness and sleep.

Effects of hypnotics

↓ sleep latency and ↑ duration of sleep.

Melatonin synthesis pathway

Tryptophan → 5-hydroxytryptophan → Serotonin → N-acetylserotonin → Melatonin.