CONICET | Buscador de Institutos y Recursos Humanos

The neural substrates of sleep and wakefulness form a highly distributed and, to some extent,redundant network, with hypocretin, monoaminergic and cholinergic systems largelypromoting wakefulness and GABAergic systems in the preoptic area, hypothalamus andbrainstem promoting sleep. The hypocretin/orexin system plays a special role in the promotionof wakefulness and suppression of REM sleep by providing excitatory input to themonoaminergic and cholinergic systems. Sleep is not a unitary state but involves a cyclicalternation between NREM and REM sleep; the pons is critical for generating the multiplecomponents (ie, EEG synchronization, eye movements and muscle atonia) that characterizeREM sleep. Recent findings have implicated the participation of hypothalamus, throughMCH/GABA that provide a critical input to pontine generator of REM sleep. The timing ofsleep and wakefulness is regulated by an interaction between the circadian pacemaker locatedin the hypothalamic SCN and a sleep homeostatic system whose anatomic location is yet to bedefinitively identified. Among various neurochemicals, extracellular AD and nNOS/NK1accumulate in the BF as wakefulness is extended and inhibits cortically projecting cholinergicneurons, thereby influencing cortical activity. In the future, it seems reasonable to expect aspreading of these insights from basic to clinical grounds for a better understanding of thecauses and mechanisms of sleep disorders and the generation of novel therapeutics in sleepmedicine