Glycinergic and GABAA-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia
Normally when people sleep, their motor pathways are inhibited so that they don’t act out their dreams. When the inhibition fails, people thrash, walk, strike out, and may harm themselves or others.
The authors of this study, Patricia L. Brooks1 and John H. Peever1,2, are looking into the mechanisms of motor inhibiition during sleep.
Summary (from the journal)
It has long been assumed that glycinergic inhibition of motor neurons is responsible for decreasing muscle tone during rapid eye movement (REM) sleep. Brooks and Peever have now overturned this hypothesis. Microdialysis of the glycine antagonist strychnine into the trigeminal nucleus of rats resulted in increased tone in facial muscle during wakefulness and non-REM sleep, suggesting that tonic glycinergic inhibition occurs during these states. Tonic inhibition immediately switched to phasic inhibition when the rat entered REM sleep, however, and although strychnine increased the size of muscle twitches, it had no effect on atonia during REM sleep. When REM ended, strychnine effects on tone reappeared. Thus it appears that contrary to assumptions, glycine decreases muscle tone in all states except REM sleep. Intriguingly, GABA antagonists and AMPA were also unable to decrease muscle tone during REM sleep, indicating that neither GABAergic inhibition nor decreased glutamatergic excitation is responsible. What is responsible for REM atonia remains a mystery.
A hallmark of rapid eye movement (REM) sleep is a potent suppression of postural muscle tone. Motor control in REM sleep is unique because it is characterized by flurries of intermittent muscle twitches that punctuate muscle atonia.
Because somatic motoneurons are bombarded by strychnine-sensitive IPSPs during REM sleep, it is assumed that glycinergic inhibition underlies REM atonia. However, it has never been determined whether glycinergic inhibition of motoneurons is indeed responsible for triggering the loss of postural muscle tone during REM sleep. Therefore, we used reverse microdialysis, electrophysiology, and pharmacological and histological methods to determine whether glycinergic and/or GABAA-mediated neurotransmission at the trigeminal motor pool mediates masseter muscle atonia during REM sleep in rats.
By antagonizing glycine and GABAA receptors on trigeminal motoneurons, we unmasked a tonic glycinergic/GABAergic drive at the trigeminal motor pool during waking and non-rapid eye movement (NREM) sleep. Blockade of this drive potently increased masseter muscle tone during both waking and NREM sleep. This glycinergic/GABAergic drive was immediately switched-off and converted into a phasic glycinergic drive during REM sleep. Blockade of this phasic drive potently provoked muscle twitch activity in REM sleep; however, it did not prevent or reverse REM atonia. Muscle atonia in REM even persisted when glycine and GABAA receptors were simultaneously antagonized and trigeminal motoneurons were directly activated by glutamatergic excitation, indicating that a powerful, yet unidentified, inhibitory mechanism overrides motoneuron excitation during REM sleep. Our data refute the prevailing hypothesis that REM atonia is caused by glycinergic inhibition. The inhibitory mechanism mediating REM atonia therefore requires reevaluation.
(Citation: J. Neurosci. 2008 28: 3535-3545; doi:10.1523/JNEUROSCI.5023-07.2008.)
Departments of 1Cell and Systems Biology and 2Physiology, Systems Neurobiology Laboratory, University of Toronto, Toronto, Ontario, Canada M5S 3G5
Correspondence should be addressed to Dr. John Peever, Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, Ontario, Canada M5S 3G5. Email: John.Peever@utoronto.ca