• Irma Rukhadze, Nancy J Carballo, Sathyajit S Bandaru, Atul Malhotra, Patrick M Fuller, and Victor B Fenik.
• Department of Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: irukhadze@ucla.edu.
• Respir Physiol Neurobiol. 2017 Oct 1; 244: 41-50.

AbstractNeural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG muscle activity during NREM sleep (F1,1,3=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG muscle activity, suggesting that A1/C1 neurons regulate upper airway patency in a state-independent manner.Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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