Schematic of the integrative model of sleep/wake regulation. An ‘integrator’ Hcrt neuron continuously integrates information from multiple and often conflicting variables, and makes the decision whether to fire and wake up the animal, or stay silent and facilitate sleep. The probability of a sleep-to-wake transition depends on (i) the functional connectivity between different sleep/wake regulatory populations, including the GABAergic neurons of the PZ, mPOA, and VLPO and dopaminergic neurons of the VTA, and (ii) internal and external factors, including sleep history, circadian phase, and predation risk. ACh, acetylcholine; BF, basal forebrain; DA, dopamine; GABA, gamma-aminobutyric acid; Glu, glutamate; Hcrt, hypocretin; His, histamine; LH, lateral hypothalamus; mPOA, medial preoptic area; NAc, nucleus accumbens; NA, noradrenaline; PZ, parafacial zone; VLPO, ventral lateral preoptic area.