The activity of the cerebral cortex is critical in determining whether sleep or wakefulness occurs, but it does not generate the drive to enter sleep or wakefulness.

This is due to the interaction of many influences, some of which are localized to specific areas of the central nervous system and others which are more diffuse (

Fig. 2.10). The most important anatomical structures concerned with sleep–wake regulation are as follows.

Ascending reticular activating system (ARAS)
The ascending reticular activating system is a physiological entity which promotes wakefulness when it is active and allows sleep when it is inhibited or inactive (

Fig. 2.6). It was originally thought to be a homogeneous system, but the complexity of its structure and function is now realized. It governs the homeostatic drive and many of the reflex components of the adaptive sleep drive, and is closely connected to the circadian sleep rhythms.

The ascending reticular activating system is largely contained in the brainstem reticular formation which is a loosely connected structure with small groups of cells and nuclei, large numbers of short interneurones and complex ascending and descending interconnecting tracts.

Most of the reticular formation lies in the central core or tegmentum of the pons and midbrain, but it also extends into the medulla, hypothalamus and thalamus. It has a complex microstructure and GABA is secreted at most of its synapses. It has an extensive influence over the sensory input to the brainstem, motor function of the cranial nerve nuclei and spinal cord, and the state of sleep or wakefulness.

It also has close links, through the hypothalamus, with endocrine control.

Nucleus of the solitary tract
This is located in the medulla and is noradrenergic. It has connections throughout the pons, hypothalamus and thalamus. It is more active in NREM sleep than in wakefulness and electrical stimulation in animals promotes sleep.

Locus coeruleus
This is situated in the upper dorsal pons and is noradrenergic. It has widespread connections in the brainstem, thalamus and basal forebrain. It is most active in wakefulness, partially suppressed in NREM sleep and inactive in REM sleep. It inhibits the activity of the LDT/PPT and is itself inhibited by GABA-ergic neurones.

Raphe nuclei
These are situated in the midline in the midbrain and are serotonergic. The most important is the dorsal raphe nucleus. The raphe nuclei are most active in wakefulness, partially suppressed in NREM sleep and inactive in REM sleep. They are inhibited by GABA-ergic neurones. They inhibit the activity of the LDT/PPT and project to the hypothalamus. They may

contribute to the autonomic and motor responses to arousal from sleep and to the emotional state.