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Posted by benfulcher on 22 Mar 2014 at 09:27 GMT
Since the discovery of the orexinergic neurons of the lateral hypothalamic area (Orx) in 1998, their crucial role in controlling arousal state, as well as a range of other functions including feeding and addiction, has been studied in great detail. The loss of Orx causes narcolepsy, a condition that affects approximately 0.05% of the population and is most typically characterized by severe daytime sleepiness and low thresholds for transitions between arousal states. However, the physiological mechanisms of Orx have yet to be linked convincingly to their behavioral manifestations. In this work we develop a reduced mathematical model of the relevant physiology and use it to explain how Orx acts to stabilize sleep and wake and thereby prevent the fragile sleep-wake balance that characterizes the narcoleptic phenotype. The model produces interpretable dynamics, generates testable predictions, and its physiological formulation is amenable to future refinement as clinical and physiological data continue to be collected. This work highlights the importance of physiologically based mathematical modeling in connecting neurological mechanisms to behavior.