Neuromodulation of hypoglossal motoneurons during sleep

Hypoglossal motoneurons are influenced by a variety of neuromodulators, some of which change dynamically across sleep–wake states to alter motoneuron excitability and responses to pharmacological manipulations. Determining the mechanisms underlying the modulation of hypoglossal motoneurons during sleep is relevant to understanding the increased upper airway resistance, airflow limitation and hypoventilation in normal sleeping individuals, as well as the airway obstruction underlying the pathogenesis of obstructive sleep apnea. This review summarizes current concepts underlying the neurobiology of sleep and arousal states, and so identifies the rationale for focus on particular neuromodulators and their effects on hypoglossal motoneurons. Emphasis is placed on the control of hypoglossal motoneurons by components of the aminergic arousal system, i.e., serotonergic, noradrenergic and histaminergic inputs. The role of inhibitory mechanisms at the hypoglossal motor nucleus, including glycine and γ-amino butyric acid, and the mixed excitatory and inhibitory influences of acetylcholine are also reviewed. New concepts on the control of hypoglossal motoneurons by sedative hypnotics are also discussed.