Orexin induces excitation of respiratory neuronal network in isolated brainstem spinal cord of neonatal rat

• We analyze effects of orexin on central respiratory control using the isolated brainstem–spinal cord preparation of newborn rats.
• Orexin produces dose-dependent increases in C4 burst rate via brainstem.
• The increases in C4 respiratory activities are associated with orexin-induced depolarization of pre-inspiratory and inspiratory neurons.

Endogenous neuropeptides known as orexins (hypocretins) play important roles in the regulation of feeding, drinking, endocrine function, and sleep/wakefulness. Orexin neuron projection sites include the rostral ventrolateral medulla of brainstem, which is related to the control of breathing. Previous studies suggest that orexins modulate the central CO2 ventilatory response during wakefulness in rodent. In the present study, we examined the effects of the orexinergic system on central respiratory control by adding orexin into a superfusion medium in the isolated brainstem–spinal cord of neonatal rat. Exposure to orexin B resulted in dose-dependent increases in C4 burst rate via brainstem, but not spinal cord. These increases in C4 burst rate induced concomitant increases in the depolarizing cycle rate of pre-inspiratory (Pre-I) and inspiratory (Insp) neurons. Tonic discharge was induced on C4 recording, although the rhythmic bursts of Pre-I and Insp neurons were maintained. Expiratory (Exp) neurons were also depolarized on administration of orexin B. Our findings indicate that orexin B activates central respiratory activity, mainly through depolarization and decreases in membrane resistance in Pre-I and Insp neurons, and possibly through early initiation of the expiratory phase induced by depolarization of Exp neurons.