title: Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition.
abstract: The depression of upper airway motor activity that develops during the rapid eye movement (REM) stage of sleep is a major factor allowing upper 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 movements and a depression of the motor output to respiratory pump and upper airway muscles. In lumbar motoneurons, the depression of activity 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 mechanisms that lead to the suppression of upper airway motoneuronal activity during REM sleep are unknown. In this study, we assessed whether the depression of hypoglossal (XII) nerve activity induced by pontine carbachol injections is caused by inhibitory amino acids acting within the XII nucleus. In decerebrate, paralyzed and artificially ventilated cats, we recorded the activities of both XII nerves (genioglossal branches), one phrenic and a cervical motor branch (to monitor postural activity). Postural atonia and respiratory depression were induced by pontine carbachol injections. The inhibitory amino acid receptor antagonists, strychnine (glycine receptors) or bicuculline (GABAA receptors), were injected (100-250 nl; 1.0-2.5 mM) into one XII nucleus (the other served as control) in an attempt to reduce or abolish the depression subsequently induced by pontine carbachol. Prior to the carbachol injections, both antagonists caused similar elevations of XII nerve activity on the treated side (30-40%). However, following carbachol, the XII nerve activity on the treated side was depressed to about 25% of the (pre-antagonist and pre-carbachol) control level, whereas the depression on the untreated side was slightly greater, to 10-15% of the control. Additional injections of antagonists during the carbachol-induced depression produced no further increase in nerve activity. This minor effect of the antagonists on the carbachol-induced depression of XII nerve activity was in contrast to the marked disinhibitory effects that both antagonists had on the XII nerve response to electrical stimulation of the lingual nerve. The latter was used as a control for the ability of strychnine and bicuculline to exert disinhibitory effects within the XII nucleus. Thus, there is little, if any, contribution of these inhibitory amino acids to the depression of XII motoneurons during the carbachol-induced, REM sleep-like postural and respiratory depression; mechanisms other than fast synaptic inhibition must be involved.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
authors.forename: L
authors.initials: L
authors.lastname: Kubin
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Tojima
authors.forename: R O
authors.initials: RO
authors.lastname: Davies
authors.forename: A I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002415:Cats; D003655:Decerebrate State; D005260:Female; D007839:Functional Laterality; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects*; D012016:Reference Values; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D009118:Muscimol; C017069:bicuculline methiodide; D002217:Carbachol; D013331:Strychnine; D001640:Bicuculline