Hypocretins and Arousal
How the brain controls vigilance state transitions remains to be fully understood. The discovery of hypocretins, also known as orexins, and their link to narcolepsy has undoubtedly allowed us to advance our knowledge on key mechanisms controlling the boundaries and transitions between sleep and wakefulness. Lack of function of hypocretin neurons (a relatively simple and non-redundant neuronal system) results in inappropriate control of sleep states without affecting the total amount of sleep or homeostatic mechanisms. Anatomical and functional evidence shows that the hypothalamic neurons that produce hypocretins/orexins project widely throughout the entire brain and interact with major neuromodulator systems in order to regulate physiological processes underlying wakefulness, attention, and emotions. Here, we review the role of hypocretins/orexins in arousal state transitions, and discuss possible mechanisms by which such a relatively small population of neurons controls fundamental brain state dynamics.
KeywordsHypocretin Narcolepsy Outputs of hypocretin neurons Probabilistic model of sleep and wake Sleep-arousal transition
- 30.Wisor J (2013) Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol 4. doi: 10.3389/Fneur.2013.00139. Artn 139
- 39.Fadel J, Deutch AY (2002) Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 111:379–387Google Scholar
- 40.Ishibashi M et al (2015) Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca(2+)-dependent resonance in LDT and PPT cholinergic neurons. Front Neurol 6:120. doi: 10.3389/fneur.2015.00120CrossRefPubMedCentralPubMedGoogle Scholar
- 43.Kohlmeier KA et al (2013) Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy. Front Neurosci 7:246. doi: 10.3389/fnins.2013.00246CrossRefPubMedCentralPubMedGoogle Scholar
- 50.Harrison NL (2007) Mechanisms of sleep induction by GABA(A) receptor agonists. J Clin Psychiatry 68(Suppl 5):6–12Google Scholar
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