Figure 12. Orexin participates in chemoreception.
The role of orexin in central chemoreception. The top panel is a schematic of a saggital section of rat brain showing the location of orexin containing neurons in the hypothalamus and their projection sites in the retrotrapezoid nucleus (RTN) and raphe magnus (RM) and raphe obscurus (Rob), which have been identified as participating in central chemoreception. The arrows point to plots demonstrating chemoreception effects at each site, At the left, the hypercapnic responses of ventilation in wild-type (WT) mice and prepro-orexin knockout mice (ORX-KO) during quiet Wakefulness are shown. Data are presented as means± SEM of five WT mice and five ORX-KO mice. *P < 0.05 compared with WT mice. At the right, the Figure shows the effects of dialysis of vehicle solution (solid circles; N= 6) and 5 mM SB-334867, an Ox1R antagonist, (open circles; N= 6) into the medullary raphe on ventilation while the rats were breathing air and 7% CO2 during wakefulness in the dark period. Mean ± SEM values are shown. The −16% effect is significant comparing vehicle to SB-334867 treatment during 7% CO2 breathing for ventilation (P < 0.001, repeated measures ANOVA interaction with gas type). In the middle, the Figure shows the effects of dialysis of vehicle solution (filled circles; n = 6) and 5 mM SB-334867 (open circles; n = 6) into the RTN on ventilation while the rats were breathing air and 7% CO2 during wakefulness. Mean ± SEM values are shown. The −30% effect is significant comparing vehicle to SB-334867 treatment during 7% CO2 breathing (P < 0.01 post hoc comparison). This composite is modified from Fig. 1 in Nattie (166) and used with permission (top panel), Fig 3 from Respiration Physiology& Neurobiology, 164, Kuwacki, Orexinergic modulation of breathing across vigilance states, 204–212, 2008, (127) and used with permission of Elsevier (bottom left panel), Fig. 2 from Respiration Physiology & Neurobiology, 170, Dias et al., The orexin receptor 1 (OX1R) in the rostral medullary raphe contributes to the hypercapnic chemoreflex in wakefulness, during the active period of the diurnal cycle, 96–102, 2010, (46) and used with permission of Elsevier (bottom right panel), and Fig. 2 in Dias et al., (47) J. Physiol. used with permission, John Wiley and Sons (bottom middle panel).