Current Topics in Medicinal Chemistry - Volume 11, Issue 19, 2011

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Sleep is clearly not only a whole-brain or global phenomenon, but can also be a local phenomenon. This accounts for the fact that the primary states of being (wakefulness, NREM sleep, and REM sleep) are not necessarily mutually exclusive, and components of these states may appear in various combinations, with fascinating clinical consequences. Examples include: sleep inertia, narcolepsy, sleep paralysis, lucid dreaming Read More

Reciprocal interactions between wakefulness and sleep substantially influence human brain function in both states of vigilance. On the one hand, there is evidence that regionally-specialized brain activity during wakefulness is modulated by the interaction between a local use-dependent buildup of homeostatic sleep pressure and circadian signals. On the other hand, brain activity during sleep, although mainly constrained Read More

Waking neurobehavioral performance is temporally regulated by a sleep/wake homeostatic process and a circadian process in interaction with a time-on-task effect. Neurobehavioral impairment resulting from these factors is taskspecific, and characterized by performance variability. Several aspects of these phenomena are not well understood, and cannot be explained solely by a top-down (subcortically driven) view of sleep/ Read More

In the present paper, we reviewed a large body of evidence, mainly from quantitative EEG studies of our laboratory, supporting the notion that sleep is a local and use-dependent process. Quantitative analyses of sleep EEG recorded from multiple cortical derivations clearly indicate that every sleep phenomenon, from sleep onset to the awakening, is strictly local in nature. Sleep onset first occurs in frontal areas, and a fr Read More

In a recent series of experiments, we demonstrated that a visuomotor adaptation task, 12 hours of left arm immobilization, and rapid transcranial magnetic stimulation (rTMS) during waking can each induce local changes in the topography of electroencephalographic (EEG) slow wave activity (SWA) during subsequent non-rapid eye movement (NREM) sleep. However, the poor spatial resolution of EEG and the difficulty of relatin Read More

Neural activity utilizes energy resources and requires replenishment of metabolites through vascular dilation. During wake, cortical neurons usually have depolarized membrane potentials and exhibit frequent spontaneous action potentials, requiring an increased metabolic delivery to activated tissue and causing blood vessels to dilate. Quiet sleep (QS) is characterized by alternating membrane potential between a depolarized a Read More

The cellular substrates of sleep are incompletely described, but historically they have been thought to be neuronal. According to one view, sleep is produced by interactions between wake-promoting neurons, sleep-inducing neurons, and sleep-inducing substances released by neurons (e.g. adenosine)[1, 2]. Alternatively, sleep pressure may arise independently among subsets of neurons in a use-dependent fashion within the Read More

This article starts with a brief review of the thalamocortical system architecture, which is composed of the projecting thalamic nuclei, the thalamic reticular nucleus, and the neocortex. Then we provide a description of the three states of vigilances followed by a detailed review of major brain rhythms present in the thalamocortical system, ranging from very slow to very fast oscillations. We provide descriptions of known mech Read More

Sleep is homeostatically regulated in all species that have been carefully studied. In mammals and birds, the best characterized marker of sleep pressure is slow wave activity (SWA), defined as the electroencephalogram (EEG) power between 0.5 and 4 Hz during NREM sleep. SWA peaks at sleep onset and decreases with time spent asleep, and reflects the synchronous firing of cortical neurons coordinated by an underlying s Read More

Our recent report demonstrated that a small subset of GABAergic interneurons in the cerebral cortex of rodents expresses Fos protein, a marker for neuronal activity, during SWS [1]. The population of sleep-active neurons consists of strongly immunohistochemically-stained cells for the enzyme neuronal nitric oxide synthase (Type I cells). By virtue of their widespread localization within the cerebral cortex and their wides Read More

The logic and potential mechanisms for a new paradigm, the local use-dependent view of sleep as a distributed dynamic process in brain, are presented. This new paradigm is needed because the current dominant top-down imposition of sleep on the brain by sleep regulatory centers is either silent or is of inadequate explanatory value for many well-known sleep phenomena, e.g. sleep inertia. Two mechanistic falsifiable Read More