2.13). This hierarchy and mutually interacting system can be broken down into the following components.
Brainstem wakefulness promoting centres
1 The aminergic nuclei, particularly the locus coeruleus, raphe nuclei and tubero-mammillary nuclei (TMN), are all most active during wakefulness, partly suppressed in NREM sleep and inactive in REM sleep.
They all promote wakefulness, inhibit the REM sleep promoting action of the LDT/PPT, and project rostrally to the thalamus, hypothalamus and basal forebrain as the ascending reticular activating system.
2 Cholinergic LDT/PPT nuclei. These promote REM sleep and are active in this state and in wakefulness, but inactive in NREM sleep . The activity of the LDT/PPT nuclei is probably the source of the highfrequency thalamocortical bursts which result in the desynchronized EEG characteristic of REM sleep.
The LDT/PPT also influence sleep-related eye movements, which are controlled by the oculo-motor nuclei, and the loss of muscle tone in REM sleep (
The difference in the combination of activity of the LDT/PPT and the aminergic nuclei between wakefulness and REM sleep is that although the LDT/PPT are active in both, the aminergic nuclei are only active in wakefulness and inactivated in REM sleep. In contrast both the aminergic and cholinergic nuclei are partially and approximately equally suppressed in NREM sleep.
Wakefulness promoting higher centres
1 The perifornical hypothalamic orexin-releasing neurones have an excitatory effect on the aminergic nuclei, promoting wakefulness, and inhibit LDT/PPT, thereby limiting the duration of REM sleep.
2 The mesolimbic dopaminergic system projects to the prefrontal cortex and limbic system, promoting wakefulness.
3 Cholinergic neurones in the basal forebrain promote wakefulness and REM sleep.
4 The suprachiasmatic nuclei have a wakefulness promoting effect, in addition to providing a circadian influence on sleep and wakefulness.