Noradrenergic modulation of hypoglossal motoneuron excitability: developmental and putative state-dependent mechanisms

Abstract

Hypoglossal (XII) motoneurons (MNs) contribute to diverse behaviors. Their innervation of the genioglossus muscle, a tongue protruder, plays a critical role in maintaining upper airway patency during breathing. Indeed, reduced activity in these motoneurons is implicated in sleep related disorders of breathing such as obstructive sleep apnea (OSA). The excitability of these MNs is modulated by multiple neurotransmitter systems. The focus of this review is on the modulation of XII MN excitability by norepinephrine (NE), which increases MN excitability through a variety of mechanisms. The level of noradrenergic drive, however, is very dynamic, varying on developmental, sleep-wake and even millisecond timescales relevant to transitions between behaviours. Here we review and provide new data on the maturation of the noradrenergic modulatory system, focusing on those elements specifically relevant to XII MN excitability including the: i) ontogeny of the noradrenergic cell group that provides the majority of the noradrenergic innervation to the XII nucleus, the Locus subcoeruleus (LsC); ii) time course over which the XII nucleus is innervated by noradrenergic nerve fibres, and; iii) ontogeny of XII MN sensitivity to NE. In the context of state-dependent changes in noradrenergic cell activity, we review mechanisms of NE action most relevant to its role in the muscle atonia of REM sleep. We conclude with a discussion of the hypothesis that the dynamics of MN modulation by NE extend to the spatial domain and recent data suggesting that noradrenergic modulation of the dendritic tree is not uniform but compartmentalized. Implications for information processing are discussed.