Adventures and tribulations in the search for the mechanisms of the atonia of REM sleep.

1473 The Background Thirty years ago, the first report was published with intracel-lular recordings from motoneurons, trigeminal motoneurons, in chronically instrumented, behaving cats across the sleep-wake cycle. A major observation was that synaptic activity, both ex-citatory and inhibitory, declined during rapid eye movement (REM) sleep in association with the characteristic motoneu-ronal hyperpolarization. However, subsequent intracellular recordings from motoneurons revealed that REM sleep was associated with the appearance of inhibitory postsynaptic potentials (IPSPs) of which some had uniquely large amplitudes. The potentials were abolished by strychnine, an antagonist of chloride dependent , fast inhibition mediated by glycine, when the drug was administered by iontophoresis into the vicinity of the recorded motoneuron. 8 These results have led to a widely accepted concept that postsynaptic, glycine-mediated inhibition is the cause of motoneuronal hyperpolarization. In another study, using an indirect approach to assess the role of inhibitory amino acids, glycine, or GABA, in the REM sleep-related suppression of trigeminal motoneurons, evidence for a contribution of active inhibition was inconclusive. Concurrently , the study provided clear evidence that neurotrans-mitters other than glycine or GABA significantly contribute to the REM sleep-related depression of motoneuronal excitabili-ty. Some of the potential mechanisms considered included a REM sleep-dependent loss of Ia afferent-mediated activation and REM sleep-related withdrawal of aminergic excitation of motoneurons. Fifteen years ago, I coauthored a study titled " Suppression of hypoglossal motoneurons during the carbachol-induced ato-nia of REM sleep is not caused by fast synaptic inhibition. " 10 We used an unanesthetized, decerebrate cat carbachol model of the atonia of REM sleep in experiments designed to test whether antagonists of glycinergic or GABA A-receptors micro-injected into the hypoglossal motor nucleus can eliminate or diminish the depression of hypoglossal nerve activity elicited by microinjections of a cholinergic agonist, carbachol, in the dorsomedial pontine reticular formation. We found that each of the two antagonists used, strychnine and bicuculline, increased the baseline level of hypoglossal nerve activity and antagonized the reflexly elicited inhibition of hypoglossal motoneurons. We also found that neither antagonist diminished the magnitude of the depression of hypoglossal nerve activity during the atonia of REM sleep. While the properties of the carbachol models of REM sleep atonia are discussed elsewhere, three aspects of the experimental design used in our 1993 study 10 are relevant for our comments on the article by Brooks and Peever. 13 First, by increasing the doses of the antagonists injected into the hy-poglossal …