Activation of Orexin B receptors in the pontine Kölliker-Fuse nucleus modulates pre-inspiratory hypoglossal motor activity in rat

Orexins (splice variants A and B) are hypothalamic neuropeptides that have essential functions in control of arousal and nutrition. Lack of Orexins is strongly associated with narcolepsy and sleep disordered breathing. However, the role of Orexins and particularly that of Orexin-B (OXB), in respiratory centres controlling upper-airway patency are less defined. In the present study we performed microinjections of OXB into the pontine Kölliker-Fuse nucleus (KF) of the dorsolateral pons, since this nucleus is particularly involved in the pre-motor control of upper airway muscles. The OXB mediated effects on heart, phrenic (PNA) and hypoglossal (XII-A) nerve activities were analysed in an in situ perfused brainstem preparation. Injection of OXB into the KF evoked significant augmentation of the respiratory frequency. Importantly, OXB provoked particularly prolonged pre-inspiratory discharge of the XII nerve, while no cardiovascular response was observed after KF microinjections.In summary, OXB in the KF exerts an excitatory effect on XII pre-motoneurones. Since pre-inspiratory activity of the XII is important for the decrease in upper airway resistance during inspiration, we conclude that OXB release in the KF has strong implications in the state-dependent control of upper airway patency under physiological and pathophysiological conditions.