Major neurotransmitters involved in the regulation of sleep-wake cycle

Neuronal activity in the central nervous system undergoes a variety of electrophysiological changes along the sleep-wake cycle. These changes are modulated by a complex interaction between different neurochemical systems located throughout the brain. Within brainstem and hypothalamus there are a number of neuronal populations that promote wakefulness through the action of different neurotransmitters like noradrenaline, serotonin, histamine and orexin. These systems act together in the generation and maintenance of wakefulness, however although each one contributes in a unique way no neurotransmitter seems to be absolutely necessary because wakefulness is not completely inhibited in the absence of any of them. On the other hand, neurons located in the hypothalamus and brainstem are involved in initiating and maintaining sleep. These neurons contain neurotransmitters such as acetylcholine and GABA and have projections to nuclei involved in wakefulness regulation. Recently, models have been proposed suggesting that sleep is modulated by flip-flop switches which are characterized by neuronal circuits with different neurotransmitters and that interacting to regulate the initiation and maintenance of the different stages of sleep wake cycle. This review is based on pharmacological, electrophysiological and neurochemical studies with the aim of analyze the major neurotransmitters and the cerebral regions involved in the regulation of wakefulness and different states of sleep.