Computational model of brain-stem circuit for state-dependent control of hypoglossal motoneurons
Abstract
In patients with obstructive sleep apnea (OSA), the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Experimental studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contributes to depression of hypoglossal motoneurons and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. In this new study, we developed a biophysical network model to test the hypothesis that, to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons needs to include excitatory and inhibitory perihypoglossal interneurons that mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. In the model, the state-dependent activation of the hypoglossal motoneurons was in qualitative agreement with in vivo data during simulated rapid eye movement (REM) and non-REM sleep. The model was applied to test the mechanisms of action of noradrenergic and serotonergic drugs during REM sleep as observed in vivo. We conclude that the proposed minimal neuronal circuit is sufficient to explain in vivo data and supports the hypothesis that perihypoglossal interneurons may mediate state-dependent monoaminergic drive to hypoglossal motoneurons. The population of the hypothesized perihypoglossal interneurons may serve as novel targets for pharmacological treatment of OSA.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2018
- Source ID
- 10.1152/jn.00728.2017
Entities
People
- Atul Malhotra
- Frank L. Powell
- Giri P Krishnan
- Irma Rukhadze
- Maxim Bazhenov
- Maxim Komarov
- Mohsen Naji
- Victor B. Fenik
Organizations
- National Heart, Lung, and Blood Institute
- National Institutes of Health
- Office of Naval Research
- University of California
- University of California, San Diego