Hypothalamus, hypocretins/orexin, and vigilance control

The hypothalamus has re-emerged as a key regulator of sleep and wakefulness, shifting the focus away from the brainstem and thalamocortical systems (ascending reticular activating systems). Several new sleep control systems in the hypothalamus and their interaction with the circadian pacemaker in the suprachiasmatic nucleus have been identified recently. More recently, deficiency of the hypothalamic peptide, hypocretin/orexin, has been found to be the major pathophysiological factor in human narcolepsy-cataplexy, the sleep disorder characterized by excessive daytime sleepiness and rapid eye movement sleep abnormalities. The results from a series of experiments suggest that the hypocretin system is involved in the maintenance of wakefulness and stabilizes the vigilance states. The hypocretin system also plays a role in the link between sleep and other fundamental hypothalamic functions, such as the regulation of food intake, metabolism, hormone release, and temperature. Sleep deprivation is known to alter hormone release, increase body temperature, stimulate appetite, and activate the sympathetic nervous system. Sleep control systems within the hypothalamus may therefore be closely integrated with homeostatic systems needed for survival. In this chapter, the role of the hypothalamus in vigilance control is discussed, with a particular emphasis on the hypocretins/orexin system.