NEURO: Sleep

Question 1

What are brain rhythms?

Answer 1

Brain rhythms can refer to distinct patterns of neuronal activity that are associated with specific behaviours, arousal level and sleep state.

The earth has a rhythmic environment that can vary with the seasons: temperature, precipitation, daylight. In order to compete effectively and survive, an animals behaviour must oscillate with its environment.

The brain has evolved a variety of systems for rhythmic control - most striking example is our sleep/wake cycle. Rhythms controlled by the brain are species dependent (e.g. hibernation).

Question 2

What is the EEG and what is it used for?

Answer 2

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

It involves non-invasive (doesn’t require incision into the body or the removal of tissue) electrodes placed on standard positions on the head - they’re connected to amplifiers and a recording device.

Today, EEGs are used primarily to help diagnose certain neurological disorders (e.g. seizures in epilepsy).

The first human EEG showed that waking and sleep EEGs are distinctly different.

Question 3

How does an EEG pick up on different levels of neuronal excitation?

Answer 3

EEGs measure the combined activity of a large number (1000s) of similarly orientated neurons (as the electrical contribution of a single neuron is very small).
The EEG requires synchronous activity across groups of cells and reflects summed post-synaptic activity of large cell ensembles.

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.

However, timing is everything - the same amount of excitation can occur at irregular intervals and result in a small summed signal.

Question 4

Describe EEG rhythms.

Answer 4

EEG rhythms correlate with various states of behaviours. They are categorised by their frequency range (named α,β,θ,δ).

High-frequency low-amplitude is associated with alertness and waking (beta and alpha).
Low-frequency high-amplitude is associated with non-dreaming sleep or coma (theta and delta).

Question 5

List the different EEG rhythm during different functional states of the brain.

Answer 5

AWAKE WITH MENTAL ACTIVITY: β 14-30 Hz

AWAKE AND RESTING: α 8-13 Hz

SLEEPING: θ 4-7 Hz

DEEP SLEEP: <3.5 δ Hz

Question 6

How is the generation of brain rhythms synchronised?

Answer 6

The activity of large groups of neurons in the cerebral cortex can produce synchronised rhythms in 2 ways:

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

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

Question 7

How do pacemakers generate synchronous brain rhythms?

Answer 7

The thalamus, with its vast input to the cerebral cortex, can act as a pacemaker. The thalamus is a large collection of nuclei located in the diencephalon and can generate rhythmic activity because of the intrinsic properties of its neurons and its synaptic interconnections.

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

Coordinated 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 8

How does collective behaviour generate synchronous rhythms?

Answer 8

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 9

What are the functions of brain rhythms?

Answer 9

Cortical rhythms parallel many interesting human behaviours.

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 activity.

However, even if brain rhythms don’t have a function, they provide us with a convenient window on the functional states of the brain (e.g. identifying neurological diseases such as epilepsy).

Question 10

What is sleep?

Answer 10

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

Question 11

What is the significance of sleep?

Answer 11

Sleep may be universal among higher invertebrates and perhaps amongst all animals (e.g. fruit fly Drosophila sleeps).
Prolonged sleep deprivation can be devastating to proper functioning.
However, we can stave off sleep… but not forever…

Question 12

What are the functional states of the brain?

Answer 12

The functional states of the brain are wakefulness and sleeping - the latter divided into 2 distinct states: Rapid Eye Movement (REM) and Non-REM sleep.

WAKEFULLNESS: associated with high frequency and low amplitude EEG pattern.

• NON-REM sleep
  Body capable of involuntary movement, rarely accompanied by vivid, detailed dreams. ‘An idling brain with moveable body’.
  EEG: high-amplitude, low frequency
• REM sleep
  Body immobilised, accompanied by vivid, detailed dreams. ‘An active, hallucinating brain in a paralysed body.’
• EEG: low-amplitude, high frequency

Question 13

Describe the sleep cycle.

Answer 13

Describe the sleep cycle.

The EEG stages can be sub-divided to
indicate depth of sleep (Stages 1-4).

Each night begins with a period of
non-REM sleep, and as night progresses, there is a shift from
non-REM to REM sleep.

Sleep stages are then cycled throughout the night, repeating ~90 minutes.

Question 14

Describe some physiological differences between NON-REM and REM sleep.

Answer 14

• Core body temperature falls more in REM sleep compared to NON-REM sleep.
• Heart rate and breathing rate falls more in NON-REM sleep compared to REM sleep.
• During REM sleep brain energy consumption (oxygen consumption) rises significantly, on the other hand brain energy consumption decreases in NON-REM sleep.

The increase/decreases above are with respect to wakefulness.

Question 15

Give a summary of the differences in behaviour during different functional states of the brain?

Answer 15

AWAKE:

• EEG: low-amplitude, high frequency
• Sensation: vivid, externally generated
• Thought: logical, progressive
• Movement: continuous, voluntary

NON-REM SLEEP:

• EEG: high-amplitude, low frequency
• Sensation: dull or absent
• Though: logical repetitive
• Movement: occasional, involuntary

REM SLEEP:

• EEG: low-amplitude, high frequency
• Sensation: vivid, internally generated
• Thought: vivid, illogical, bizarre
• Movement: muscle paralysis, movement commanded by the brain but not carried out

Question 16

Why do we sleep?

Answer 16

We don’t really know. No single theory of the function of sleep is widely accepted, although most reasonable ideas fall into 2 categories: theories of restoration and adaption.

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

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

Question 17

What is the neural mechanism of wakefulness?

Answer 17

During wakefulness, there is an increase in brain stem activity.

Several sets of neurons increase rate of firing in anticipation of wakening and enhance the wake state. These include:

• ACh from the basal forebrain
• Hypocretin (orexin) from the lateral hypothalamus
• Histamine from the midbrain.
• 5-HT from the raphe nucleus
• NA from the locus coeruleus

Collectively, these neurons synapse directly on the thalamus and cerebral cortex and other brain regions.

This leads to neuronal depolarisation and an increase in excitatory activity, which suppresses rhythmic forms of firing in the thalamus and cerebral cortex present during sleeping.

Question 18

How do neural mechanisms alter in sleep?

Answer 18

During sleep, there is a decrease in brain stem activity.

Several sets of neurons decrease rate of firing during sleep. These include:

• ACh from the basal forebrain
• 5-HT from the raphe nucleus
• NA from the locus coeruleus

Cholinergic neurons in the pons are shown to increase the rate of firing to induce REM sleep - linked with dreaming (ACh from midbrain and pons). Neurons in the pons activate several areas of the cerebral cortex that can illicit memories an emotions.

Several sets of neurons firing during wakefulness suppresses the rhythmic firing in the thalamus. The absence of this allows for rhythmic forms of firing in the thalamus leading to the blocking of the flow of sensory information to the cortex during sleep.

However, other sleep-promoting factors also involved in promoting sleep…

Question 19

What are the 4 main sleep promoting factors?

Answer 19

• Adenosine
• Melatonin
• Nitric Oxide
• Inflammatory Factors

Question 20

How does adenosine promote sleep?

Answer 20

Adenosine is a building block used by cells for DNA, RNA and ATP.

Adenosine receptor (neuromodulation) activation decreases heart rate, respiratory rate and smooth muscle tone (decreasing blood pressure).

Adenosine has an inhibitory effect on ACh, NA, and 5-HT thus promotes sleep.

Adenosine receptor antagonists (e.g. caffeine) promote wakefulness.

Question 21

How does Nitric oxide promote sleep?

Answer 21

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

Question 22

How do inflammatory factors promote sleep?

Answer 22

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 – this may be evidence for the adaptation theory.

Question 23

How does melatonin promote sleep?

Answer 23

Melatonin is a hormone secreted by then pineal gland at night. It is shown to initiate and maintain sleep. It can be found in over-the-counter medication for symptoms of insomnia and jet-lag.

Question 24

What are circadian rhythms.

Answer 24

A circadian rhythm refers to any rhythm with a period of approximately 24 hours.

Almost all land animals coordinate 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 25

If daylight and darkness cycles are removed from an animal’s environment, what will happen to and what determines the circadian rhythms?

Answer 25

If cycles of daylight and darkness are removed from an animal’s environment, circadian rhythms continue.

Primary clocks for circadian rhythms are biological (“brain clocks”).

Question 26

What are zeitgebers?

Answer 26

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 27

What is the Suprachiasmatic Nucleus (SCN)?

Answer 27

The suprachiasmatic nucleus (SCN) is our biological clock.

The SCN is a small nucleus of the hypothalamus that receives retinal innervation and synchronises circadian rhythms with the daily light-dark cycle. There are 2 SCNs located just above the optic chiasm.

Question 28

What happens when the SCN is removed from animals?

Answer 28

With no SCN, animals had fluctuating sleep and temperature - no pattern.

SCN inhibition does not abolish sleep – animals will continue to coordinate sleep with light-dark cycles if they are present.

Question 29

How do neurons in the SCN regulate circadian rhythms?

Answer 29

SCN clock genes produce proteins that send feedback to the SCN and cause a decrease in gene transcription and therefore inhibit further production of proteins - occurs over a 24 hour period (is thus a circadian process).

Light information from the retina serves to rest the SCN neuron clocks each day.

SCN has control over circadian clocks throughout the body - impacting the ANS,
core body temperature, hormone control and feeding, metabolism and locomotion which in turn regulate other clocks such as that in the liver.

Question 30

What cells are responsible for sycnhronising the SCN to the circadian rhythms?

(From older years)

Answer 30

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.

Question 31

Glossary

Answer 31

The electroencephalogram – A method of measuring electrical activity in the brain
Rapid eye movement (REM) sleep – A kind of sleep that occurs at intervals during the night and is characterised by rapid eye movements, more dreaming and bodily movement, and faster pulse and breathing.
Non-REM sleep – A period of sleep characterized by decreased metabolic activity, slowed breathing and heart rate, and the absence of dreaming.
Circadian rhythm – The ‘body clock’: a cycle that tells our bodies when to sleep, rise, and eat, regulating many physiological processes
Zeitgeber - A rhythmically occurring natural phenomenon which acts as a cue in the regulation of the body’s circadian rhythms.
Suprachiasmatic nucleus - A pair of small nuclei in the hypothalamus of the brain, above the optic chiasma, thought to be concerned with the regulation of physiological circadian rhythms.