SUPPRESSION OF HYPOGLOSSAL MOTONEURONS DURING THE CARBACHOL-INDUCED ATONIA OF REM-SLEEP IS NOT CAUSED BY FAST SYNAPTIC INHIBITION

The depression of upper airway motor activity that develops during the rapid eye movement (REM) stage of sleep is a major factor allowing up per airway obstructions to occur in patients with sleep apnea syndrome . Microinjections of carbachol, a cholinergic agonist, into the dorsal pontine tegmentum of chronically instrumented cats produce REM sleep. In acutely decerebrate cats, carbachol induces postural atonia, eye m ovements and a depression of the motor output to respiratory pump and upper airway muscles. In lumbar motoneurons, the depression of activit y is due to a glycinergic inhibition that has the same characteristics during natural REM sleep in chronic cats and carbachol-induced atonia in decerebrate cats (Neurophysiology, 57 (1987) 1118-1129). The mecha nisms that lead to the suppression of upper airway motoneuronal activi ty during REM sleep are unknown. In this study, we assessed whether th e depression of hypoglossal (XII) nerve activity induced by pontine ca rbachol injections is caused by inhibitory amino acids acting within t he XII nucleus. In decerebrate, paralyzed and artificially ventilated cats, we recorded the activities of both XII nerves (genioglossal bran ches), one phrenic and a cervical motor branch (to monitor postural ac tivity). Postural atonia and respiratory depression were induced by po ntine carbachol injections. The inhibitory amino acid receptor antagon ists, strychnine (glycine receptors) or bicuculline (GABA(A) receptors ), were injected (100-250 nl; 1.0-2.5 mM) into one XII nucleus (the ot her served as control) in an attempt to reduce or abolish the depressi on subsequently induced by pontine carbachol. Prior to the carbachol i njections, both antagonists caused similar elevations of XII nerve act ivity on the treated side (30-40%). However, following carbachol, the XII nerve activity on the treated side was depressed to about 25% of t he (pre-antagonist and pre-carbachol) control level, whereas the depre ssion on the untreated side was slightly greater, to 10-15% of the con trol. Additional injections of antagonists during the carbachol-induce d depression produced no further increase in nerve activity. This mino r effect of the antagonists on the carbachol-induced depression of XII nerve activity was in contrast to the marked disinhibitory effects th at both antagonists had on the XII nerve response to electrical stimul ation of the lingual nerve. The latter was used as a control for the a bility of strychnine and bicuculline to exert disinhibitory effects wi thin the XII nucleus. Thus, there is little, if any, contribution of t hese inhibitory amino acids to the depression of XII motoneurons durin g the carbachol-induced, REM sleep-like postural and respiratory depre ssion; mechanisms other than fast synaptic inhibition must be involved .