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Following studies of patients with postinfluenza encephalitis, the neuropathologist von Economo reported that inflammatory lesions of the preoptic area (POA) were often associated with insomnia and therefore proposed that the POA was critical for the production of normal sleep [1]. Then, Ranson in monkeys, Nauta in rats, and McGinty in cats showed that POA lesions induce a profound and persistent...
The hypocretins (Hcrts) – also known as “orexins” – are a pair of neuropeptides well known for their role in promoting wakefulness. Shortly after their discovery, multiple laboratories identified the crucial link between dysfunction of the Hcrt system and narcolepsy in mice, dogs, and humans [1–6]. Therefore, much research has focused on the wake-promoting properties of Hcrts and why their absence...
In mammals, sleep is commonly defined as “a rapidly reversible state of (behavioral) immobility and greatly reduced sensory responsiveness to environmental stimuli” [1]. Sleep and wake states have been strongly conserved during evolution, and “sleep-like” states exist in most organisms, including worms, flies, and fish [2], suggesting common underlying neural circuits and endocrine systems. During...
It is eminently clear from numerous chapters in this volume that the orexin (hypocretin) neuropeptides are necessary for the normal expression of waking and sleep. However, it remains fundamentally unclear how the absence of signaling by these peptides results in the symptoms of narcolepsy. Which of the many neurons bearing orexin receptors are necessary to sustain normal waking and sleep, and which...
Since the discovery of the hypocretins (Hcrt) [1] or orexins [2] and the subsequent link to narcolepsy in animals [3, 4] and humans [5, 6] a decade ago, it has become apparent that the Hcrt system plays a central role in a number of physiological and behavioral functions. The well-established clinical symptomatology of narcolepsy including excessive daytime sleepiness and cataplexy gave rise to the...
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...
Mathematical modeling offers a way to critically test experimentally derived theories, integrate experimental results across spatial and temporal scales, and generate predictions to drive bench science and influence clinical practice. Although, in general, mathematical modeling approaches have been applied to narcolepsy only recently, developments in modeling normal sleep/wake behavior have laid an...
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