Figure 2: Highlights of neurochemistry of sleep–wake cycle. (A) Mechanism favoring wakefulness: Orexin from lateral hypothalamus excites several wake promoting regions such as locus coeruleus (LC), ventral tegmental area (VTA), tuberomammillary nucleus (TMN), and raphe nucleus. These regions result in cortical excitability through several neurotransmitters such as noradrenaline (NA), dopamine (DA), histamine (HA), and serotonin (5-HT), respectively. At the same time, cholinergic neurons in the pedunculopontine and laterodorsal tegmental areas (PPT/LDT) activate many forebrain targets, including the thalamus, which eventually contribute to cortical excitability and wakefulness. (B) Neurons of the ventrolateral preoptic area (VLPO) produce γ-aminobutyric acid (GABA) and galanin and inhibit all the arousal systems during non-rapid eye movement (NREM) sleep. Cells in and near LDT/PPT release acetylcholine (Ach) in thalamus during rapid eye movement (REM) sleep; thus activating it and producing cortical desynchrony. The switching of NREM–REM sleep is thought to depend on mutually inhibitory REM-off and REM-on areas modulated by GABAergic neurons located mainly in mesopontine tegmentum