title: The neuro-biomolecular basis of alertness in sleep disorders.
abstract: Sleep is present in all species in which it has been studied, but its functions remain unknown. Identification of the molecular correlates of sleep and wakefulness is essential if we are to understand the restorative processes that occur during sleep, the cellular mechanisms that underlie sleep regulation, and the functional consequences of sleep loss and poor quality sleep. To address the questions of how we know whether sleep has performed its functions and whether treatment has improved sleep quality, we have proposed a synaptic homeostasis hypothesis about the significance of slow wave activity (SWA) during sleep and its homeostatic regulation. Briefly, the hypothesis states that (1) wakefulness is associated with potentiation in several cortical circuits; (2) synaptic potentiation is then tied to the homeostatic regulation of SWA; (3) SWA is associated with synaptic downscaling; and (4) synaptic downscaling is tied to the beneficial effects of sleep on performance. According to this hypothesis, the potentiation of neural circuits that results from synaptic plasticity during alert wakefulness is responsible for SWA homeostasis. Increasing noradrenergic activity increases the expression of long-term potentiation (LTP)-related genes, and interference with these changes block the induction of markers of synaptic potentiation during alert wakefulness. Inducing local LTP-like changes during alert wakefulness also results in increased local slow wave homeostasis. Thus, as SWA homeostasis can be induced on a local level or can be triggered by a learning task, and is strongly correlated with postsleep performance enhancement, plasticity during alert wakefulness depends on good sleep, which, in turn, depends on efficient synaptic downscaling.
authors.affiliation: Department of Psychiatry, University of Wisconsin, Madison, USA. gtononi@wisc.edu
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
mesh_terms: D000818:Animals; D001143:Arousal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D008959:Models, Neurological; D009638:Norepinephrine / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses
chemical_list: D009638:Norepinephrine