Sleep

Question 0

What are the important inputs that promote wakefulness?

Answer 0

Wakefulness is promoted by excitatory input:

• directly to cortical neurons or indirectly via thalamocortical projections.
• Important direct inputs to cortex arise from
  (a) basal forebrain nuclei (cholinergic),
  (b) hypothalamic nuclei arise from
  (a) basal forebrain nuclei (cholinergic),
  (b) hypothalamic nuclei (various transmitters),
  (c) ascending projections from upper brainstem nuclei (dorsal raphe nuclei, locus coeruleus; monoamine transmitters)
  (d) especially from the reticular formation which also activates (noradrenaline and aceylcholine) thalamic neurons that project to cortex.

Question 1

How does wakefulness work in terms of the thalamocortical relationship?

Answer 1

Wakefulness depends on the relationship between activity in the thalamus and in the cortex.

Cortical and thalamic activity is mutually interactive.
When relatively hyperpolarized, thalamic neurons fire in ‘phasic’ bursts that drive low frequency ‘synchronized’ (delta wave) activity in the cortex that correlates with sleep.

When they are depolarized, thalamic neurons fire high frequency ‘tonic’ activity that drives ‘desynchronized’ activity (beta/gamma wave) in cortical networks that correlates with wakefulness

Question 2

What comments of the reticular activating system are you aware of?

Answer 2

Upper brain stem nuclei and the reticular formation are components of an ascending Reticular Activating System (aRAS)

Question 3

Wake – nREM Sleep transition (hypnagogic transition) uses a hypothalamic ‘flip-flop’ mechanism. What do you know about this?

Answer 3

The lateral (LNH) and posterior (PNH) nuclei of the hypothalamus project to and excite (orexin as transmitter) the brainstem aRAS nuclei which in turn feed back to excite (monoamines noradrenaline and 5HT) the hypothalamic neurons.

Activation of this loop ‘flips’ the system into high aRAS activity.

The VLPO (ventrolateral preoptic ) inhibits (GABAergic) aRAS nuclei which leads to disinhibition of the VLPO causing increased VLPO activity and more inhibition so the system ‘flops’ into low aRAS activity