Sleep and Circadian Rhythms

Question 1

Why has the brain evolved a variety of systems?

Answer 1

The earth has a rhythmic environment – temperature, precipitation and daylight vary with the seasons.

In order to compete effectively and survive, an animals behaviour must oscillate with it’s environment.

The brain has evolved a variety of systems for rhythmic control – most striking example is our sleep/wake cycle.

Question 2

How do we measure brain rhythmicity?

Answer 2

Using electroencephalogram (EEG)

Question 3

What is EEG?

Answer 3

The electroencephalogram (EEG) is a measurement of electrical activity generated by the brain and recorded from the scalp.

Question 4

What does the EEG involve?

Answer 4

Involves non-invasive electrodes placed on standard positions on the head – connected to amplifiers and a recording device.

Question 5

What is the EEG used for today?

Answer 5

Today, the EEG is used primarily to help diagnose certain neurological disorders (e.g. seizures in epilepsy).

Question 6

How does the EEG work?

Answer 6

EEG measures the combined activity of a large number (1000s) of similarly orientated neurons

Question 7

What does the EEG require?

Answer 7

Requires synchronous activity across groups of cells.

Question 8

What does the EEG reflect?

Answer 8

EEG reflects summed post-synaptic activity of large cell ensembles.

Question 9

What does the amplitude of the EEG depend on?

Answer 9

The amplitude of an EEG signal depends upon how synchronous the activity of the neurons is.

When a group of cells is excited the tiny signals sum to generate a large surface signal.

Timing is everything – the same amount of excitation can occur, but at irregular intervals resulting in a small summed signal.

Question 10

What do EEG rhythms correlate to?

Answer 10

EEG rhythms correlate with states of behaviours.

EEG rhythms are categorised by their frequency range.

Question 11

What is a high frequency low amplitude associated with?

Answer 11

alertness and waking

Question 12

What is low frequency high amplitude associated with?

Answer 12

non-dreaming sleep or coma

Question 13

How are synchronous brain rhythms generated?

Answer 13

Synchronous rhythms can be led by a central clock or pacemaker (e.g. thalamus).

Synchronous rhythms can arise from the collective behaviour of cortical neurons themselves.

Question 14

How does the thalamic pacemaker work?

Answer 14

The thalamus, with its vast input to the cerebral cortex, can act as a pacemaker.

Synaptic connections between excitatory and inhibitory thalamic neurons force each individual neuron to conform to the rhythm of the group.

Co-ordinated rhythms are then passed to the cortex by thalamocortical axons.

Thus, a relatively small group of centralised thalamic cells can compel a much larger group of cortical cells.

Question 15

How does the collective behaviour of cortical neurons generate synchronous brain rhythms?

Answer 15

Some rhythms of the cerebral cortex do not depend on a thalamic pacemaker – rely instead on collective interactions of cortical neurons themselves.

Excitatory and inhibitory interconnections of neurons result in a co-ordinated, synchronous pattern of activity.

This can remain localised or spread to encompass larger regions of the cortex.

Question 16

What are the functions of brain rhythms?

Answer 16

One plausible hypothesis is that most brain rhythms have no direct function – instead they are by-products.

Brain circuits are strongly interconnected with various forms of excitatory feedback – rhythms may be an unavoidable consequence of such circuitry.

However, even if brain rhythms don’t have a function, they provides us with a convenient window on the functional states of the brain.

Question 17

What is sleep?

Answer 17

Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment.

Sleep may be universal among higher invertebrates and perhaps amongst all animals (e.g. fruit fly Drosophila sleeps).

Question 18

Do we need sleep?

Answer 18

Prolonged sleep deprivation can be devastating to proper functioning.

However, we can stave off sleep… but not forever

Question 19

What are the functional states of the brain?

Answer 19

Wakefulness

Non-REM sleep: Body capable of involuntary movement, rarely accompanied by vivid, detailed dreams.

REM sleep: Body immobilised, accompanied by vivid, detailed dreams.

Question 20

What is the difference between non-REM and REM sleep?

Answer 20

Non-REM sleep: 
Temp ↓
HR ↓ ↓
Breathing ↓ ↓
Brain energy consumption ↓

REM sleep:
Temperature ↓ ↓ ↓
Heart rate ↓ (irregular)
Breathing ↓ (irregular)
Brain energy consumption ↑↑↑

Question 21

Compare the EEG between the states of the brain

Answer 21

Awake: low-amplitude, high frequency

Non-REM: high amplitude, low frequency

REM: low-amplitude, high frequency

Question 22

Compare sensation between the states of the brain

Answer 22

Awake:
vivid, externally generated

non-REM:
dull or absent

REM:
vivid, internally generated

Question 23

Compare thought between the states of the brain:

Answer 23

Awake:
Logical, progressive

non-REM:
Logical, repetitive

REM:
vivid, illogical, bizzare

Question 24

Compare movement between the states of the brain

Answer 24

Awake:
continuous, voluntary

non-REM:
occasional, involuntary

REM:
muscle paralysis: movemet commanded by the brain but not carried out

Question 25

Compare REM between the different states of the brain

Answer 25

Awake: often non-REM: rare REM: often

Question 26

What is the sleep cycle?

Answer 26

EEG stages can be sub-divided to indicate depth of sleep (Stages 1-4). Each night begins with a period of non-REM sleep. Sleep stages are then cycled throughout the night, repeating approximately every 90 minutes As night progresses, there is a shift from non-REM to REM sleep.

Question 27

What can the theories on the purpose of sleep be split up to?

Answer 27

No single theory of the function of sleep is widely accepted, although most reasonable ideas fall into two categories – theories of restoration and adaptation.

Question 28

What is the theory of restoration?

Answer 28

We sleep to rest and recover and to prepare to be awake again.

Question 29

What is the theory of adaptation?

Answer 29

We sleep to protect ourselves (e.g. hide from predators) and to conserve energy.

Question 30

What are the neural mechanisms of wakefulness?

Answer 30

During wakefulness, there is an increase in brainstem activity. Several sets of neurons increase rate of firing in anticipation of wakening and enhance the wake state (e.g. ACh, 5-HT, NE and histamine). Collectively, these neurons synapse directly brain regions including the thalamus and cerebral cortex. Increase in excitatory activity supresses rhythmic forms of firing in the thalamus and cortex present during sleep.

Question 31

What are the neural mechanisms of sleep?

Answer 31

During sleep, there is an decrease in brainstem activity. Several sets of neurons decrease rate of firing during sleep (e.g. ACh, 5-HT and NE). However, cholinergic neurons in pons shown to increase rate of firing to induce REM sleep. Rhythmic forms of firing in the thalamus shown to block the flow of sensory information up to the cortex. However, other sleep-promoting factors also involved in promoting sleep…

Question 32

What are the 4 sleep promoting factors?

Answer 32

Adenosine nitric oxide inflammatory factors melatonin

Question 33

Describe adenosine as a sleep-promoting factor.

Answer 33

Adenosine is a building block for DNA, RNA and ATP. Adenosine receptor activation decreases heart rate, respiratory rate and smooth muscle tone (decreasing blood pressure). Adenosine receptor antagonists (e.g. caffeine) promote wakefulness.

Question 34

Describe nitric oxide as a sleep-promoting factor

Answer 34

Nitric oxide (NO) is a potent vasodilator. Decreases smooth muscle tone (decreasing blood pressure). NO also stimulates adenosine release.

Question 35

Describe inflammatory factors as a sleep-promoting factor

Answer 35

Sleepiness is a familiar consequence of infection (e.g. cold, flu). Cytokines (e.g. interleukin-1) stimulates the immune system to fight infections. Interleukin-1 levels shown to promote non-REM sleep –evidence for adaptation theory?

Question 36

Describe melatonin as a sleep-promoting factor.

Answer 36

Melatonin is a hormone secreted by the pineal body at night. Over-the-counter medication for symptoms of jet-lag. Shown to initiate and maintain sleep – role in natural sleep-wake cycle remains unclear.

Question 37

What are circadian rhythms?

Answer 37

Almost all land animals co-ordinate behaviour according to circadian rhythms – the daily cycles of daylight and darkness that result from the spin of the Earth. Most physiological processes also rise and fall with daily rhythms (e.g. temperature, hormone levels).

Question 38

What is so interesting about if cycles of daylight and darkness are removed from an animal's environment?

Answer 38

If cycles of daylight and darkness are removed from an animals environment, circadian rhythms continue. Primary clocks for circadian rhythms are biological (“brain clocks”).

Question 39

What are zeitgebers?

Answer 39

Environmental time cues (e.g. light-dark, temperature, humidity) are collectively termed zeitgebers. It is quite difficult to separate a human from all possible zeitgebers – even inside a laboratory (e.g. people coming/going provide time cues). Isolation studies are therefore best conducted in deep caves. If humans are separated from all possible zeitgebers, they are said to be in a “free-running” state – internal biological clock of approximately 24.5-25.5 hours.

Question 40

What is the SCN?

Answer 40

The suprachiasmatic nucleus (SCN) is a small nucleus of the hypothalamus that receives retinal innervation and synchronises circadian rhythms with the daily light-dark cycle. SCN inhibition does not abolish sleep – animals will continue to co-ordinate sleep with light-dark cycles if they are present.

Question 41

Explain SCN mechanisms

Answer 41

Retinal cells synchronising the SCN are not rods or cones – they are specialised photoreceptor cells expressing the photopigment melanopsin. Photoreceptors expressing melanopsin are slowly excited by light and can detect changes in luminosity. Project directly to the SCN, inhibiting the production of melatonin by the pineal gland – melatonin involved in inducing the onset of sleep.