Hypocretins and the neurobiology of sleep-wake mechanisms

In 1998, our group discovered a cDNA that encoded the precursor of two putative neuropeptides that we called hypocretins for their hypothalamic expression and their similarity to the secretin family of neuropeptides. In the past 15 years, numerous studies have placed the hypocretin system as an integrator of homeostatic functions with a crucial, nonredundant function as an arousal stabilizer. Here, we discuss some of the data that have accumulated over the years on the integrating capacity of these hypothalamic neurons and their role on sleep-to-wake transitions.