Sleep basics Electrophysiological recordings of human brain reveal three distinct state of existence: wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. The distinction between sleep and wakefulness is attributed to the synchronization and desynchronization of thalamocortical circuits.6,7 Wake-like or “desynchronized” (low-amplitude and high-frequency) electroencephalographic

(EEG) activity with clusters of REM and very low levels of muscle tone characterize REM sleep. NREM sleep includes all sleep except REM sleep, and is by convention divided into four stages corresponding to increased depth of sleep as indicated by the progressive dominance of “synchronized” Inhibitors,research,lifescience,medical EEG activity (also known as low-voltage high-amplitude delta or slow-wave activity); in this respect, sleep stages 3 and 4 are collectively labelled as delta sleep or slow-wave sleep (SWS). Inhibitors,research,lifescience,medical Recurrent cycles of NREM and REM sleep of about 90 min characterize

normal human sleep. In the successive cycles of the night, the duration of stages 3 and 4 decrease, and the proportion of the cycle occupied by REM sleep tends to increase. The REM episodes occurring late in the night have more eye movement bursts than REM episodes occurring early Inhibitors,research,lifescience,medical in the night.8 Sleep-wake alternation is classically viewed as resulting from the interaction of two regulating processes (circadian-C and homeostatic-S).9 The propensity to sleep or be awake at any given time is a consequence of a sleep debt (process S) and its interaction with Inhibitors,research,lifescience,medical wake-promoting signals coming from the circadian clock (process C) located in the suprachiasmatic nucleus (SCN). This wake-promoting signal opposes the sleep need, which progressively increases from morning awakening, ensuring an even degree of alertness throughout the day.10 At sleep onset, an imbalance between the two opposing influences favor sleep-promoting Inhibitors,research,lifescience,medical signals, and the sleep need and its electrophysiological signature, slow-wave activity,

is at its highest level. Throughout sleep Amisulpride and up to final morning awakening, there is a progressive decline in slow-wave activity reflected by an increase in REM sleep proportion across successive REM/NREM cycles. During the last decade, research lent support to the idea that three interacting neuronal systems (a wakepromoting system, an NREM-promoting system, and a REM-promoting system) are involved in this complex regulation construct. Different structures sending widespread cortical projection and located in the brain stem, the hypothalamus, and the basal forebrain check details constitute the wake-promoting or arousal system (Figure 1).11,12 Glutamatergic brain stem reticular neurons, cholinergic neurons of the basal forebrain, and monoaminergic transmission are largely implicated in the arousal system.