The discovery in
1998-99 of hypocretin/orexin and its role in the development
of narcolepsy in animal models and in humans revolutionized
our understanding of this debilitating disorder and promises
important advances in the diagnosis and therapy of human narcolepsy.
Discovery of the neuromodulatory role of hypocretin/orexin also
greatly improved our understanding of the basic neurobiologic
processes that control sleep and wakefulness. Anatomic areas
promoting sleep such as the ventrolateral preoptic (VLPO)
area of the hypothalamus have also been characterized.
New anatomical and physiological approaches have led to advances
in our understanding of the location and interconnections between
hypothalamic and brainstem circuits controlling REM, nonREM,
and wake states. Factors regulating the activity of these sleep-controlling
neurons have been identified. Circuitry and neurotransmitter
mechanisms controlling muscle tone across the sleep cycle, of
relevance to numerous sleep pathologies, have also been identified.