Article

Saper CB, Chou TC, Scammell TE: The sleep switch: Hypothalamic control of sleep and wakefulness

Dept of Neurology, Program in Neuroscience, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Trends in Neurosciences (Impact Factor: 12.9). 01/2002; 24(12):726-31. DOI: 10.1016/S0166-2236(00)02002-6
Source: PubMed

ABSTRACT More than 70 years ago, von Economo predicted a wake-promoting area in the posterior hypothalamus and a sleep-promoting region in the preoptic area. Recent studies have dramatically confirmed these predictions. The ventrolateral preoptic nucleus contains GABAergic and galaninergic neurons that are active during sleep and are necessary for normal sleep. The posterior lateral hypothalamus contains orexin/hypocretin neurons that are crucial for maintaining normal wakefulness. A model is proposed in which wake- and sleep-promoting neurons inhibit each other, which results in stable wakefulness and sleep. Disruption of wake- or sleep-promoting pathways results in behavioral state instability.

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    • "Internally, the sleep–wake rhythm is centrally coordinated by an endogenous circadian clock, placed in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus (Maywood et al., 2006). The neurons of the SCN are circadian oscillators that form functional pacemakers (Saper et al., 2001; Cheng et al., 2002). The timing of their oscillations is determined by an intrinsic cellular rhythmicity, which lasts 24 h, even in the absence of external inputs (Moore et al., 2002) such as light, feeding patterns, and social environment (Mueller et al., 2013). "
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    • "During the wake stage, orexin neurons send stimulating signals to depolarize the ''arousal center'' [59] [79]. This has been demonstrated by in vitro and in vivo experiments. "
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    • "Orexin antagonists have been considered as potential treatments for various disorders including addiction, depression and anxiety (Pich and Melotto, 2014; Yeoh et al., 2014). The orexinergic neurons of the lateral hypothalamus modulate monoaminergic and cholinergic projections implied in cortical arousal (Saper et al., 2001). Thus, the effects of orexin on sleep dysfunction in affective disorders could be mediated by differential effects on monoamine-cholinergic imbalance and these in turn help determine the changes in EEG profile. "
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