Figure 2.
Schematic drawing showing main projections of orexin neurons. This figure summarizes predicted orexinergic projections in the human brain. Please note that distributions of orexin fibers and receptors (OX1R, OX2R) are predicted from the results of studies on rodent brains since most histological studies on the orexin system have been carried out in mice and rats. Circles show regions with strong receptor expression and dense orexinergic projections. Orexin neurons originating in the lateral hypothalamic area (LHA) and posterior hypothalamus (PH) regulate sleep and wakefulness and the maintenance of arousal by sending excitatory projections to the entire CNS, excluding the cerebellum, with particularly dense projections to monoaminergic, and cholinergic nuclei in the brain stem and hypothalamic regions including the locus coeruleus (LC, containing noradrenaline), tuberomammillary nucleus (TMN, containing histamine), raphe nuclei (Raphe, containing serotonin), and laterodorsal/pedunclopontine tegmental nuclei (LDT/PPT), containing acetylcholine). Orexin neurons also have links with the reward system through the ventral tegmental area (VTA, containing dopamine) and with the hypothalamic nuclei that stimulate feeding behavior.