Figure 1.

Orexin neurons project throughout the brain to promote and maintain wakefulness. Orexin neurons in the lateral hypothalamus project to the major arousal-promoting nuclei, including neurons producing histamine (HA; tuberomammillary nucleus), norepinephrine (NE; e.g., locus ceruleus), serotonin (5-HT; e.g., dorsal raphe), dopamine (DA; e.g., ventral tegmental area), and acetylcholine (Ach; e.g., basal forebrain, pedunculopontine and laterodorsal tegmental nuclei). The orexin neurons provide direct, excitatory inputs to the cortex, thalamus, and spinal cord. In addition, the orexin neurons may be autoexcitatory.