Sagittal scheme of the rat brain illustrating hypocretinergic influences on the cerebral cortex and wakefulness-promoting structures. Hypocretin/orexin (Hcrt/Orx) hypothalamic neurons send axons to both the cerebral cortex and neurochemically-specific neuronal groups projecting to the cortex, which are most involved in wakeulness maintenance and cortical activation. These groups are the noradrenergic locus coeruleus (LC), serotonergic dorsal raphe nucleus (RDo), cholinergic laterodorsal tegmental (LDT) and peduculopontine tegmental (PPT) nuclei, dopaminergic ventral tegmental area (VTA), histaminergic tuberomammilary nucleus (TMN) and cholinergic basal forebrain (BF) In the pontine tegmentum, Hcrt/Orx axons reach DOPT, where Hcrt/Orx enhance wakeulness, and also vRPO, where Hcrt/Orx suppress REM. Figure modified from [19].