Grant: Operating Grant

Obstructive sleep apnea (OSA) is a serious health issue, affecting more than 4% of individuals. It is characterized by repeated episodes (hundreds) of airway blockage and apnea (periods when breathing stops) during the night. OSA patients suffer from excessive daytime sleepiness, are at great risk for accidents and at high risk for cardiovascular disease. A major factor in OSA is that during sleep, especially dreaming sleep, muscles of the airway undergo almost complete relaxation because regions of the brain that normally keep these muscles active shut-down. When you try to breathe in, the negative pressure in the airway pulls the airway muscles, especially the tongue, backwards which blocks the airway. A major focus of research in OSA has been on the motoneurons that control the tongue muscle and how their activity changes with sleep-wake cycling. The ultimate objective of this work is to find ways to increase tongue muscle activity in sleep to prevent OSA. The activity of the tongue muscle, however, is not just determined by the activity tongue motoneurons but by a whole circuit that transmits activity from regions in the brain the generate breathing, through an intermediate group of neurons called premotoneurons that ultimately communicate with the motoneurons. As with motoneurons, reduced activity of these premotoneurons during sleep could be an important contributor to OSA. However, virtually nothing is known about these premotoneurons because they are widely dispersed amongst many other neurons and extremely difficult to find. We have recently identified a molecular marker for these neurons that has been used to engineer mice in which these neurons light up under a fluorescent light. Therefore, the objective of this study is to use these engineered mice to learn as much as possible about these neurons so that we can develop strategies to manipulate them in naturally sleeping animals and understand how they contribute to airway control in sleep.