The Neural Basis of Sleepiness in Narcoleptic Mice

Abstract

(from the chapter) Everyone with narcolepsy has some degree of daytime sleepiness, and for most, sleepiness is the symptom of greatest concern. This chronic sleepiness is often severe and can substantially impair relationships, the ability to drive safely, and performance at school and work. Although it is now clear that narcolepsy with cataplexy is caused by an extensive and selective loss of the orexin/hypocretin-producing neurons, remarkably little is known about how this results in chronic sleepiness. Several pathophysiological processes have been proposed to underlie the sleepiness of narcolepsy. These mechanisms include reduced activity of wake-promoting brain regions; inadequate inhibition of sleep-promoting systems; enhanced homeostatic sleep drive; impaired circadian promotion of wakefulness; and poor quality, nonrestorative sleep. All of these hypotheses have their strengths, but they have been difficult to test fully in clinical studies. In this chapter, we will discuss how mouse models of narcolepsy have provided novel insights into the pathophysiology of excessive daytime sleepiness in narcolepsy. The Appendix to this chapter contains a general discussion of using mice in sleep research. (PsycINFO Database Record (c) 2012 APA, all rights reserved).