AUTHOR=Varga Adrienn G. , Whitaker-Fornek Jessica R. , Maletz Sebastian N. , Levitt Erica S. TITLE=Activation of orexin-2 receptors in the KÓ§lliker-Fuse nucleus of anesthetized mice leads to transient slowing of respiratory rate JOURNAL=Frontiers in Physiology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.977569 DOI=10.3389/fphys.2022.977569 ISSN=1664-042X ABSTRACT=

Orexins are neuropeptides originating from the hypothalamus that serve broad physiological roles, including the regulation of autonomic function, sleep-wake states, arousal and breathing. Lack of orexins may lead to narcolepsy and sleep disordered breathing. Orexinergic hypothalamic neurons send fibers to KÓ§lliker-Fuse (KF) neurons that directly project to the rostroventral respiratory group, and phrenic and hypoglossal motor neurons. These connections indicate a potential role of orexin-modulated KF neurons in functionally linking the control of wakefulness/arousal and respiration. In a reduced preparation of juvenile rats Orexin B microinjected into the KF led to a transient increase in respiratory rate and hypoglossal output, however Orexin B modulation of the KF in intact preparations has not been explored. Here, we performed microinjections of the Orexin B mouse peptide and the synthetic Orexin 2 receptor agonist, MDK 5220, in the KF of spontaneously breathing, isoflurane anesthetized wild type mice. Microinjection of Orexin-2 receptor agonists into the KF led to transient slowing of respiratory rate, which was more exaggerated in response to Orexin-B than MDK 5220 injections. Our data suggest that Orexin B signaling in the KF may contribute to arousal-mediated respiratory responses.