Orexin/hypocretin plays a role in the response to physiological disequilibrium

In the decade since the discovery that pathology of the orexin/hypocretin system is causative for the sleep disorder narcolepsy, considerable progress has been made in understanding the functional role of the neuropeptide. Two, apparently separate functions of orexin have emerged as a consensus from studies to date. The first is the effect on vigilance state boundaries, as exemplified by narcolepsy. Thus the absence of orexin severely limits the ability to maintain prolonged periods of wakefulness or sleep and also allows the unregulated appearance of cataplexy as sudden muscle weakness during wakefulness. The second function is that orexin acts as a signaling molecule in transferring information about physiological disequilibrium to the central nervous system. Orexin activates the central arousal and motor systems during such disequilibrium and so may facilitate the necessary response and adaptation to restore equilibrium. A feasible relationship between these two functions is therefore that the maintenance of prolonged and active wakefulness is an integral part of this adaptive process. Furthermore, the limit placed on the onset of sleep by orexin suggests that these adaptive processes then continue during sleep to become integrated into the development of a coping strategy for the longer term.