Grant: Travel Awards - Institute Community Support

Obstructive Sleep Apnea (OSA) is a serious health issue, affecting >10% of individuals and prevents those afflicted from getting a good night's sleep. It is characterized by repeated episodes (hundreds per night) of airway obstruction and apnea (no airflow) that cause recurrent decreases in blood oxygen, elevations of carbon dioxide, and frequent awakenings. OSA patients experience excessive daytime sleepiness, a diminished quality of life and increased risk of cardiovascular disease and industrial accidents. Treatments options are few and not always well tolerated. Development of pharmacological therapies is limited by a poor understanding of the neurochemical mechanisms underlying the loss of tone (atonia) in upper airway muscles during sleep. Hypoglossal (XII) motoneurons control airway muscles that play a central role in OSA. During wakefulness their activity is high, which prevents airway collapse. During sleep a change in the balance of neurochemicals causes motoneuron activity to fall, muscle tone to decrease and, in predisposed individuals, the airway to collapse. Potential mechanisms underlying reduced motoneuron activity are activation of neurons that release inhibitory neurochemicals and turn off the motoneurons (active inhibition), or the "turning off" in sleep of neurons that release excitatory neurochemicals (disfacilitation). However, the mechanism of atonia in XII motoneurons remains controversial. Here, we investigate whether a mechanism of modulating excitability, and thus a potential mechanism for disfacilitation, in XII motoneurons, i.e. persistent inward currents, is significantly affected by the neurochemicals that change with sleep-wake state. Our results indicate that there is a small effect of these neurochemicals on the persistent inward currents in neonatal animals and an increased effect in juvenile animals. Further research will be needed to assess the therapeutic potential of these findings for OSA treatments.