Abstract
The hypocretin (Hcrt), also known as orexin, peptides are essential for arousal stability. Here we discuss background information about the interaction of Hcrt with other neuromodulators, including norepinephrine and acetylcholine probed with optogenetics. We conclude that Hcrt neurons integrate metabolic, circadian and limbic inputs and convey this information to a network of neuromodulators, each of which has a different role on the dynamic of sleep-to-wake transitions. This model may prove useful to predict the effects of orexin receptor antagonists in sleep disorders and other conditions.
Highlights
Transitions between states of vigilance have long been associated with changes in cortical excitability associated with changes in the activity of monoamines and neuromodulators (Steriade, 2003). Steriade and McCarley (1990), Steriade et al (1993), Steriade (2003) performed intracellular recordings of cortical neurons in different brain states and proposed that the concerted activity of norepinephrine, histamine, acetylcholine, and glutamate was sufficient to induce a sleep-to-wake transition
The mechanisms underlying the precise coordination of sleep states have remained poorly understood
THE HYPOCRETINS/OREXINS: CRITICAL REGULATORS OF AROUSAL STABILITY Soon after their discovery in 1998, two groups described the association between Hcrt deficiency and the sleep disorder narcolepsy (Chemelli et al, 1999; Lin et al, 1999; Nishino et al, 2000, 2001; Peyron et al, 2000; Thannickal et al, 2000)
Summary
Transitions between states of vigilance have long been associated with changes in cortical excitability associated with changes in the activity of monoamines and neuromodulators (Steriade, 2003). Steriade and McCarley (1990), Steriade et al (1993), Steriade (2003) performed intracellular recordings of cortical neurons in different brain states and proposed that the concerted activity of norepinephrine, histamine, acetylcholine, and glutamate was sufficient to induce a sleep-to-wake transition. Several studies have shown that the Hcrt knockout (KO) or Hcrt-R2 deficient (Mochizuki et al, 2011) mice have normal amounts of sleep and wakefulness across the light/dark cycle (Mochizuki et al, 2004) but exhibit an increased instability of behavior states.
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