Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep‐like depression of hypoglossal motoneuronal activity

Abstract

SUMMAR Y Recently, we reported that the suppression of hypoglossal (XII) motoneuronal activity that occurs during the carbachol-induced, rapid eye movement (REM) sleep-like state is abolished by the microinjection into the XII nucleus of a drug mix that antagonizes aminergic excitation and amino acid-mediated inhibition (prazosin, methysergide, bicuculline and strychnine). We now assess the role of glycinergic inhibition in the depression of XII motoneuronal activity and estimate the distribution of the antagonists around the XII nucleus at the time when they are effective. Towards the first goal, REM sleep-like episodes were elicited in urethane-anesthetized rats by 10 nl carbachol microinjections into the dorsomedial pons prior to, and at different times after, combined microinjections into the XII nucleus of only three antagonists (strychnine omitted). As in our previous study, the carbachol-induced depression of XII activity was abolished during tests performed 42-88 min after the antagonists, whereas other characteristic effects of carbachol (appearance of hippocampal theta, cortical activation, decreased respiratory rate) remained intact. The depressant effect of carbachol on XII motoneurons partially recovered after 2.5 h. Towards the second goal, using a drug diffusion model, we determined that the tissue concentrations of the antagonists at the time when they were effective were within the range of their selective actions, and the drugs acted within 0.9-1.4 mm from the injection sites, thus within a space containing XII motoneurons and their dendrites. We conclude that antagonism of a-adrenergic, serotonergic, and GABA A receptors are sufficient to abolish the REM sleep-like atonia of XII motoneurons.

Selective Loss of Catecholaminergic Wake–Active Neurons in a Murine Sleep Apnea Model

“…Catecholaminergic neurons in A1/C1, A5, A7, and to a lesser extent locus ceruleus, innervate upper airway motoneurons (Rukhadze and Kubin, 2007). Noradrenergic innervation of upper airway motoneurons contributes to activation of upper airway dilator motoneurons (Lai et al, 2001;Fenik et al, 2005;Chan et al, 2006;Rukhadze and Kubin, 2007). However, in our studies, at least the A5 and A7 groups appear relatively unperturbed by hypoxia/reoxygenation exposures.…”

Application of histamine or serotonin to the hypoglossal nucleus increases genioglossus muscle activity across the wake–sleep cycle

“…Second, extracellular levels of NE are reduced in the HMN during induced PS-like atonia (Lai et al, 2001). Finally, injection of the selective a 1 -adrenoceptor antagonist prazosin into the HMN reduces HMN nerve activity in urethane-anaesthetized rats (Fenik et al, 2005a). Recently, it has been shown that, in freely behaving rats, microdialysis application of terazosin, an a 1 -and a 2B -adrenoceptor antagonist, to the HMN reduces both respiratoryrelated and tonic GG activities during W, whereas application of phenylephrine, a specific a 1 -adrenoreceptor agonist, increases GG muscle activity during W and SWS, but not during PS (Chan et al, 2006).…”

Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

“…After completion of the 15-min observation period following the last PE injection and an additional interval of 37 Ϯ 4 (SD) min, PZ was injected successively at three sites (40 nl each) targeting the XII nucleus at three rostrocaudal levels to antagonize ␣ 1-adrenoceptors in the entire XII nucleus in 10 shamand 7 CIH-treated rats. The first injection was placed at the same coordinates used for the PE injections, followed by one injection 0.65 mm caudal and one injection 0.65 mm rostral to the first one (14,15). The three PZ injections were completed within 8.0 Ϯ 0.5 (SE) min.…”