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This chapter focuses on the neurotransmitter and neuromodulator systems involved in the regulation of wakefulness and sleep as well as the neurochemical responses to sleep loss. Wakefulness, rapid eye movement (REM), and non-REM (NREM) states were originally defined in mammals using measures of skull surface electrical brain activity, skeletal muscle activity, and eye movements. The two primary factors that determine the degree of human vigilance and sleepiness are the duration of prior wakefulness and circadian influences. Increases in homeostatic sleep need are associated with subjective sleepiness, objective sleepiness, diminished neurocognitive function, as well as neurochemical and neurophysiological changes. The ascending reticular activating system (ARAS) is comprised of the brainstem reticular formation and its ascending projections responsible for cortical activation and wakefulness. Electrophysiological and neurochemical data indicate that highest levels of orexinergic activity occur during active wakefulness, and greatly reduced activity is seen during NREM and REM sleep.
In this chapter, we will review the recent developments relevant to understanding the neural systems that regulate REM sleep. We will review the initial discovery of REM sleep, followed by a brief description of the polysomnographic characterization of REM sleep. Our discussion will continue with a review of the principal brain-stem executive neurons responsible for REM generation. Pontine reticular formation neurons are involved in the expression of the majority of REM-sleep phenomena, including low-amplitude/high-frequency cortical EEG, the hippocampal theta rhythm, PGO waves/P-waves, and muscle atonia. Cholinergic brain-stem neurons are REM-on, promoting REM sleep; and serotonergic and noradrenergic brain-stem neurons are REM-off, suppressing REM sleep. GABAergic and glutamatergic mechanisms are also integral to REM sleep control. We will also survey the prominent nuclei of the midbrain and forebrain that promote, but do not generate, REM-sleep expression. The conclusion of this chapter will provide a review of three prominent models of REM-sleep regulation: the reciprocal-interaction model; the REM sleep “flip-flop” circuit model; and the revised model of paradoxical (REM) sleep control proposed by Luppi and colleagues.
This chapter begins with an overview of the neural systems involved in vigilance state regulation. The first successfully recorded electrical activity of the human brain highlighted that the profile of electroencephalograms is changed across the vigilance states. Wakefulness is characterized by a cortical EEG profile of low-voltage, fast/high-frequency field potentials of the alpha, beta, high beta, and gamma spectral range. Non-rapid eye movement (NREM) sleep may be classified into three stages according to recent criteria of the American Academy of Sleep Medicine (AASM). The field of sleep medicine has seen a recent investigational surge, due to the development of novel experimental techniques, as well as an increased public awareness of sleep disorders and their implications. All human life, and indeed the life of most animals, is shaped by periods of wakefulness and sleep, and thus knowledge of the underlying mechanisms is of great biological, social, and medical significance.
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