Sleep and Circadian Rhythms (neuro)

Question 1

Brain rhythms

Answer 1

• Brain rhythms 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

Question 2

The electroencephalogram (EEG)

Answer 2

• The electroencephalogram (EEG) is a measurement of electrical activity generated by the brain and recorded from the scalp.
• The first human EEG was described in 1929 – Hans Berger showed that waking and sleep EEGs are distinctly different
• Involves non-invasive electrodes placed on standard
  positions on the head – connected to amplifiers and a
  recording device
• Today, the EEG is used primarily to help diagnose
  certain neurological disorders (e.g. seizures in epilepsy)
• EEG measures the combined activity of a large number (1000s) of similarly orientated neurons
• Requires synchronous activity across groups of cells
• EEG reflects summed post-synaptic activity of large cell ensembles
• The amplitude of an EEG signal depends upon how synchronous the activity of a group of cells is
• When a group of cells are excited and synchronous, 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 3

EEG rhythms

Answer 3

• EEG rhythms can be categorised by their frequency range:
  • A high-frequency low-amplitude associated with alertness and waking
  • A low-frequency high-amplitude associated with non-dreaming sleep

Question 4

Generation of synchronous brain rhythms

Answer 4

• pacemaker: synchronous rhythms can be led by a central clock or pacemaker (eg thalamus)
• collective behaviour: aynchronous rhythms can arise from the collective behaviour of cortical neurons themselves

Question 5

Thalamic pacemaker

Answer 5

• 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 neurons can compel a much larger group of cortical neurons

Question 6

Collective behaviour of cortical neurons

Answer 6

• 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 cerebral cortex

Question 7

Functions of brain rhythm

Answer 7

• 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 (e.g. epilepsy)

Question 8

Sleep

Answer 8

• Sleep is a readily reversible state of reduced responsiveness to, and interaction with, the environment.
• Prolonged sleep deprivation can be devastating to proper functioning
• Sleep may be universal amongst all animals (e.g. fruit fly Drosophila sleeps)
• However, we can stave off sleep… but not forever…

Question 9

Functional states of the brain

Answer 9

• wakefulness
• non-REM sleep: body capable of involuntary movement, rarely accompanied by vivid, detailed dreams, “Idling brain in a moveable body”
• REM sleep: body immobilised, accompanied by vivid,
  detailed dreams, “An active, hallucinating brain in a paralysed body”

Question 10

The Sleep Cycle

Answer 10

• EEG rhythms 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 11

Non-REM sleep vs REM sleep

Answer 11

non-REM sleep:
- temperature drops (1)
- heart rate drops (2)
- breathing drops (2)
- brain energy consumption drops (1)
REM sleep:
- temperature drops (3)
- heart rate drops (1) (irregular)
- breathing drops (1) (irregular)
- brain energy consumption increases (3)

Question 12

Summary for sleep and wakefulness

Answer 12

Behaviour -> awake -> non-REM sleep -> REM sleep

• EEG -> low amplitude; high frequency -> high amplitude; low frequency -> low amplitude; high frequency
• Sensation -> vivid, externally generated -> dull or absent -> vivid, internally generated
• Thought -> logical, progressive -> logical, repetitive -> vivid, illogical, bizarre
• Movement -> continuous, voluntary -> occasional, involuntary -> muscle paralysis: movement commanded by the brain but not carried out

Question 13

Why do we sleep?

Answer 13

• No single theory of the function of sleep is widely accepted, although most reasonable ideas fall into two categories – theories of restoration and adaptation.
• Restoration - sleep allows to rest and recover and to prepare to be awake again
• Adaption - sleep allows to protect ourselves (eg hide from predators) and to conserve energy

Question 14

Neural mechanisms of wakefulness

Answer 14

• 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, norepinephrine 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 15

Neural mechanisms of sleep

Answer 15

• 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 norepinephrine)
• Rhythmic forms of firing in the thalamus shown to block the flow of sensory information up to the cortex
• However, cholinergic neurons in pons shown to increase rate of firing to induce REM sleep – linked with dreaming
• However, other sleep-promoting factors also involved in promoting sleep…

Question 16

Sleep-promoting factors

Answer 16

• Adenosine:
  • 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)
  • Inhibitory effect on ACh, norepinephrine and 5-HT, which promote wakefulness
  • Adenosine receptor antagonists (e.g. caffeine) promote wakefulness
• Nitric oxide (NO):
  • Nitric oxide (NO) is a potent vasodilator
  • Decreases smooth muscle tone (decreasing blood pressure)
  • NO also stimulates adenosine release
• Inflammatory factos:
  • 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?
• Melatonin:
  • Melatonin is a hormone secreted by the pineal gland at night
  • Shown to initiate and maintain sleep
  • Over-the-counter medication for symptoms of insomnia and jet-lag

Question 17

Circadian rhythms

Answer 17

• A circadian rhythm refers to any rhythm with a period of approximately 24 hours.
• If cycles of daylight and darkness are removed from an
  animals environment, circadian rhythms continue
• 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)
• Primary clocks for circadian rhythms are biological (“brain
  clocks”)

Question 18

Brain clocks

Answer 18

• 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 19

Suprachiasmatic nucleus (SCN)

Answer 19

• 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 20

Suprachiasmatic nucleus (SCN) mechanisms

Answer 20

• If individual neurons from the SCN are isolated and grown in culture, their activity (e.g. rate of firing) continues as they would within the SCN
• SCN clock genes produce proteins that send feedback to the SCN and inhibit further production of those proteins –
  occurs over a period of 24 hours
• Light information from the retina serves to rest the SCN neuron clocks each day
• SCN has control over circadian clocks throughout the body (e.g. liver)