Neurochemical regulation of the states of alertness.

Sleep and wakefulness are two active states of the central nervous system, and sleep is further subdivided into two components: orthodox sleep (OS) and paradoxical sleep (PS). The relationships between sleep and wakefulness are asymmetrical inasmuch as wakefulness can override sleep whereas the converse occurs much more rarely. This probably indicates that sleep and wakefulness are mediated by different sorts of neurotransmitter systems. The types of neurotransmission, and the concepts of cotransmitter and neuromodulation are briefly outlined. The role of particular wiring of some neurones is also relevant in the understanding vigilance regulation. Activation of catecholamine pathways is coincident with wakefulness and deactivation is one of the conditions necessary for sleep to take place. The induction of PS is also positively related to brain catecholaminergic activity; the level of activation of these systems appears, however, to be lower during PS than during wakefulness. Serotonin, once thought to be the main transmitter in sleep, now appears to regulate the synthesis of yet unidentified sleep factors, responsible for OS and PS realization. Cholinergic mechanisms are also involved in wakefulness and in PS triggering. Such mechanisms may be part of the switch between wakefulness and PS, possibly by controlling the level of catecholaminergic activity. Gamma-aminobutyric acid also participates in the vigilance states, and benzodiazepines exert hypnogenic effects by modulating gamma-aminobutyric acid transmission. Sleep factors and hypnogenic peptides probably exist, but none of the substances so far described can yet be identified as the critical component in the subtle and still largely elusive mechanisms of vigilance regulation.