Impact of brainstem sleep mechanisms on pharyngeal motor control

Suppression of respiratory muscle activity in sleep, particularly evident in the pharyngeal muscles, is pivotal to the pathogenesis of common sleep-related breathing disorders such as obstructive sleep apnea. Obstructive apneas are caused by sleep-related decrements in pharyngeal muscle activity that leads to snoring and airway obstruction in individuals with underlying structural narrowing of the upper airway. Since obstructive apneas occur exclusively during sleep, this disorder by definition is state-dependent and ultimately caused by the influences of brainstem sleep mechanisms on pharyngeal motoneurons in individuals with compromised upper airway anatomy. This paper reviews the central neuronal mechanisms by which sleep reduces the output to the pharyngeal muscles and the neurotransmitters implicated in this alteration. The experimental approaches used to address this problem are also mentioned and their relative advantages and disadvantages discussed. In particular, the information derived from reduced animal preparations is reviewed and the need for studies in natural sleep is emphasised. Identifying the central neuronal mechanisms and neurotransmitters involved in sleep-related suppression of pharyngeal muscle activity not only has important basic relevance to understanding state-dependent respiratory control, it also has immediate clinical relevance to understanding common sleep-related breathing disorders at the central neuronal level. Determining these basic mechanisms also has immediate clinical relevance to understanding the pathogenesis of airway occlusions, and guiding neuro-pharmacological approaches aimed at preventing the sleep-related decrements in pharyngeal muscle tone that are ultimately the root cause of obstructive sleep apnea.