Figure 7.

Schematic illustration of presumed pathways underlying orexin actions on NREM and REM sleep. Orexins activate histaminergic (His)/GABAergic (GA), serotonergic (5HT), noradrenergic (NA), and cholinergic (ACh) neurons, as well as GABAergic and neurochemically unidentified (not shown in this figure for simplicity) putative interneurons, in wake-promoting nuclei, including the TMN, DR/MnR, LDT/PPT, and LC. These neurons differentially express OX₁R and/or OX₂R and regulate wakefulness/NREM sleep and NREM/REM sleep transitions. OX₁R and OX₂R may be expressed in the same populations of GABAergic neurons, as shown in the figure, or may be expressed in distinct populations of these neurons in each area. Wake/REM-on cholinergic neurons (ACh/W) are likely to suppress NREM sleep but REM-on cholinergic neurons (ACh/R) are likely to induce REM sleep. Wake-active serotonergic and noradrenergic neurons in the DR/MnR and LC, respectively, counteract activation of REM-on cholinergic neurons in the LDT/PPT, as well as REM-on neurons in the brainstem reticular formation (Sakurai et al., 1998; Pace-Schott and Hobson, 2002). Previous reports have suggested contributions of GABAergic interneurons inhibiting PPT cholinergic and raphe serotonergic neurons (Liu et al., 2002; Takakusaki et al., 2005). LHA, Lateral hypothalamic area; PH, posterior hypothalamus.