A diagram summarizing the fast neurotransmitter systems that appear to play the largest role in promoting wakefulness, based on results of lesions and opto- and chemogenetic excitation and inhibition. Note that the monoaminergic, cholinergic, and peptidergic neurons in the brainstem and hypothalamus, which were prominent in earlier models, are here shown in brown as they appear to play a modulatory role, but lesions in these locations have little effect on wake-sleep amounts. The backbone of the arousal system in this model, shown in red, is the glutamatergic input from the parabrachial nucleus (PB) and pedunculopontine tegmental nucleus (PPT) to the basal forebrain, and the GABAergic and cholinergic neurons in the basal forebrain (BF) that diffusely innervate the cerebral cortex. Lesions at these sites cause complete loss of consciousness, whereas lesions of supramammillary (SUM) glutamatergic neurons or dopaminergic (DA) neurons in the ventral periaqueductal gray matter (vPAG) near the dorsal raphe nucleus cause about a 20% loss of wake time. In addition, two populations of GABAergic neurons in the lateral hypothalamus (LH), shown in purple, have recently been proposed to promote wakefulnes by inhibiting sleep promoting neurons in the thalamus and preoptic area. Abbreviations: 5HT, serotonin; Ach, acetylcholine; Hist, histamine; LC, locus coeruleus; LDT, laterodorsal tegmental nucleus NA, noradrenlaine; ORX, orexin; TMN, tuberomammillary nucleus Modified with permission from [].