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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    ABSTRACT: Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.
    Frontiers in Cellular Neuroscience 03/2015; 9:140. DOI:10.3389/fncel.2015.00140 · 4.18 Impact Factor
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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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    ABSTRACT: There is a strong correlation between signature EEG frequency patterns and the relative levels of distinct neuromodulators. These associations become particularly evident during the sleep-wake cycle. The monoamine-acetylcholine balance hypothesis is a theory of neurophysiological markers of the EEG and a detailed description of the findings that support this proposal are presented in this paper. According to this model alpha rhythm reflects the relative predominance of cholinergic muscarinic signals and delta rhythm that of monoaminergic receptor effects. Both high voltage synchronized rhythms are likely mediated by inhibitory Gαi/o-mediated transduction of inhibitory interneurons. Cognitively, alpha and delta EEG measures are proposed to indicate automatic and flexible strategies, respectively. Sleep is associated with marked changes in relative neuromodulator levels corresponding to EEG markers of distinct stages. Sleep studies on memory consolidation present some of the strongest evidence yet for the respective roles of monoaminergic and cholinergic projections in declarative and non-declarative memory processes, a key theoretical premise for understanding the data. Affective dysregulation is reflected in altered EEG patterns during sleep.
    Frontiers in Neuroscience 04/2014; 8:63. DOI:10.3389/fnins.2014.00063 · 3.70 Impact Factor
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