Ventilation and Neurochemical Changes During µ-Opioid Receptor Activation or Blockade of Excitatory Receptors in the Hypoglossal Motor Nucleus of Goats

Authors

Thomas M. Langer, Medical College of Wisconsin
Suzanne E. Neumueller, Medical College of Wisconsin
Emma Crumley, Medical College of Wisconsin
Nicholas J. Burgraff, Medical College of Wisconsin
Sawan Talwar, Medical College of Wisconsin
Matthew R. Hodges, Medical College of Wisconsin
Lawrence Pan, Marquette UniversityFollow
Hubert V. Forster, Medical College of Wisconsin

Document Type

Article

Language

eng

Publication Date

8-24-2017

Publisher

American Physiological Society

Source Publication

Journal of Applied Physiology

Source ISSN

0021-8987

Abstract

Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally (n = 5) or bilaterally (n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala², N-MePhe⁴, Gly-ol]enkephalin (DAMGO; 100 µM) decreased pulmonary ventilation (V̇i), breathing frequency (f), and genioglossus (GG) muscle activity but did not alter neuromodulators measured in the effluent mCSF. However, neither unilateral dialysis of a broad spectrum muscarinic receptor antagonist (atropine; 50 mM) nor unilateral or bilateral dialysis of a mixture of excitatory receptor antagonists altered V̇i or GG activity, but all of these did increase HMN serotonin (5-HT) levels. Finally, during night studies, DAMGO and excitatory receptor antagonist decreased ventilatory variables during NREM sleep but not during wakefulness. These findings contrast with previous dialysis studies in the ventral respiratory column (VRC) where unilateral DAMGO or atropine dialysis had no effects on breathing and bilateral DAMGO or unilateral atropine increased V̇i and f and decreased GABA or increased 5-HT, respectively. Thus we conclude that the mechanisms of compensatory neuromodulation are less robust in the HMN than in the VRC under physiological conditions in adult goats, possibly because of site differences in the underlying mechanisms governing neuromodulator release and consequently neuronal activity, and/or responsiveness of receptors to compensatory neuromodulators.

Comments

Accepted version. Journal of Applied Physiology, Vol. 123 (August 24, 2017): 1532-1544. DOI. © 2017 the American Physiological Society. Used with permission.

Recommended Citation

Langer, Thomas M.; Neumueller, Suzanne E.; Crumley, Emma; Burgraff, Nicholas J.; Talwar, Sawan; Hodges, Matthew R.; Pan, Lawrence; and Forster, Hubert V., "Ventilation and Neurochemical Changes During µ-Opioid Receptor Activation or Blockade of Excitatory Receptors in the Hypoglossal Motor Nucleus of Goats" (2017). Physical Therapy Faculty Research and Publications. 146.
https://epublications.marquette.edu/phys_therapy_fac/146