Pontine A7 and A5 noradrenergic neuronal groups mediate long‐term facilitation of hypoglossal motor activity induced by episodic airway obstruction

Abstract

In obstructive sleep apnea (OSA), decreased noradrenergic activation of genioglossus muscle during REM sleep results in repetitive upper airway occlusion, a neurodegenerative process that aggravates with age. Episodic end‐expiratory airway occlusion simulating OSA in anesthetized rats has been shown to induce a vagally‐mediated and noradrenergic‐dependent long‐term facilitation (LTF) of genioglossus muscle activity (Tadjalli et al, J Neurosci, 2010). To identify the brainstem noradrenergic pathways mediating this effect, we applied episodic end‐expiratory tracheal occlusion (10 sec x 12 episodes) in 6 urethane‐anesthetized rats to induce genioglossus LTF and reveal corresponding cFos expressions in the affected brainstem pathways, in comparison to 3 control rats in which tracheal occlusion was not performed. We found that the percentage of cFos immunopositive neurons was significantly higher in A7 and A5 noradrenergic groups in experimental rats than that in control rats (32.9±5.3% vs. 0.7±0.7% for A7 and 34.8±7.2% vs. 5.4±5.4% for A5, P<0.01), while the expression of cFos was not significantly changed in A6 (locus coeruleus) and other medullary noradrenergic groups. In the second group of experiments, we examined the LTF induction after inhibition of A7 or A5 by microinjection of α2‐adrenoreceptor agonist clonidine. We found that after inhibition of either A7 (n=8) or A5 (n=4), the induction of genioglossus LTF was blocked. These studies demonstrated that the pontine noradrenergic neuronal groups A7 and A5 played a key role in the vagally‐mediated genioglossus LTF which, once fully developed, may help to defend against recurrent OSA. (Supported by HL093225)