ELM 20 - Rhythms and sleep

What is the ultradian rhythm?

Minutes, hours, seconds

What is infradian rhythm?

Monthly

What is the Suprachiasmatic nucleus?

Directly connected to eyes

• Melanopsin

Light detected by receptors in retine, transferred along RHT (retinohypothalamic tract) to SCN

What is the organisation of the SCN?

Pair of nuclei side by side with 10,000 neurons each

What does the core SCN do?

Processes info, adjusts circadian rhythm. Recieve info from eyes

What neuropeptides does the core SCN have?

VIP - vasointestinalpolypeptide

What function and neuropeptides does the shell SCN have?

• Send outputs to other brain areas. Synchronises other organs and rest of body

• AVP (arginine vasopressin)

What is the molecular clock?

A bunch of genes called clock genes expressed in a rhythmic fashion

What generates circadian rhythms in neuronal function?

Circadian expression of clock genes within SCN neurons

What is melatonin secreted by?

Pineal gland which is indirectly connected to SCN

What is sleep hormone?

Melatonin

How is melatonin synthesised?

Tryptophan

What time are most people alert?

10AM

When do heart related problems tend to happen?

morning

When is pain/ osteoarthritis worse?

Afternoon

What is chronopharmacology the study of?

• manner and extent to which kinetics and dynamics of medication affected by endogenous biological rhythms

• dosing time of meds affects biological timekeeping and features

What is oxaliplatin?

First cancer chrono drug

• mean and max dose increased by 15% if given in circadian rhythm modulated rate

• approved for colorectal cancer

What is lithium treatment for?

Bipolar

What can lithium medication cause?

• Affects number of circadian genes, activation of clock transcription

• Lithium causes period lengthening and phase delay of sleep/wake body temp rhythms

What are problems associated with sleep deprivation?

Cognitive, performance and immune system impairment

What is the deepest stage of sleep?

NREM3

What happens during NREM3 sleep stage?

Slow wave delta sleep

• Body repairs and regrows tissues

• Builds bone, muscle, repairs immune system

How is sleep regulated?

• Brain areas controlling sleep

• Drive to sleep and cricadian clock

• External factors

What is encephalatis lethargica?

People sleep for 20 hours a day

• Epidemic after WW1

• Causing virus never identified

Where were legions on brain found in encephalatis lethargica?

• Midbrain and diencephalon

What is the flip flop switch model?

When we’re awake, learning areas of brain most active.

Sleep promoting areas most active - inhibit brain for promoting wakefulness

What parts of the brain promote wakefulness ?

• LC

• TMN

• Raphe

What parts of the brain promote sleep?

VLPO

eVLPO

What governs sleep and wakefulness?

• circadian alerting signal

• homeostatic drive to sleep

What external factors influence sleep?

• Light

• Jet lag and shift work

• Pain, stress, medical conditions

• Medications or other substances

• Sleep environment

What neuropeptide is involved in sleep ?

Orexin

• Produced by small number of neurons in hypothalamus

How does orexin act?

Acts on Hcrtr2 (GPCR) in target tisssues

What is narcolepsy?

Sleep disorder, result of autoimmune attack destroying orexin producing neurons

What other animal can narcolepsy occur in?

Dogs - premature stop codon in Hcrtr2 receptor (inherited)