Unraveling the Mechanisms of REM Sleep Atonia

WE THANK THE EDITORS1 FOR THIS FORUM AND THE COMMENTATORS2–6 FOR THEIR DISCUSSION OF OUR WORK.7 WE AGREE WITH THE COMMENTATORS that determining mechanisms of rapid eye movement (REM) sleep motor atonia is of major scientific importance and clinical relevance. The concept that REM atonia is under the control of one physiological mechanism and one neurotransmitter pathway has seduced many of us. The undoubted appeal of the current theory—that glycinergic inhibition of motoneurons is the only mechanism mediating REM atonia—is its inherent simplicity. However, the fact that several laboratories now provide evidence indicating that glycinergic inhibition plays only a minimal role in mediating REM atonia7–9 and that other neurotransmitter pathways contribute to motor suppression in REM sleep10–13 indicates that we need to reevaluate mechanisms of REM atonia. If glycinergic inhibition is indeed the dominating force driving motor inhibition during REM sleep, then why does blockade of glycine receptors at the trigeminal motor pool not prevent REM atonia in masseter muscles?7 Our work demonstrates that antagonism of glycine and GABAA receptors at the trigeminal motor pool causes a profound increase in masseter muscle tone during both wakefulness and non-rapid eye movement (NREM) sleep; however, this same intervention does not prevent or even reverse REM atonia, despite the fact that it potently provokes muscle-twitch activity in REM sleep (Figure 1). In fact, REM atonia persists even when glycine and GABAA receptors are blocked and potent glutamatergic agonists are simultaneously applied to the trigeminal motor pool. We interpret these findings to indicate that (1) glycinergic- and GABAA-mediated inhibition plays a minimal role in triggering REM atonia; (2) inhibition primarily functions to suppress muscle twitches during REM sleep; and, (3) a powerful, yet unidentified, inhibitory mechanism or mechanisms override excitation during REM sleep. Some commentators offer alternative possibilities for our experimental observations; we respond to these discussion points below. Figure 1 Blockade of glycine and GABAA receptors at the trigeminal motor pool does not prevent masseter muscle atonia during REM sleep. A. Typical EMG and EEG traces illustrating that strychnine/bicuculline perfusion into the left trigeminal motor pool increases ...

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