title: Identification of the transmitter and receptor mechanisms responsible for REM sleep paralysis.
abstract: During REM sleep the CNS is intensely active, but the skeletal motor system is paradoxically forced into a state of muscle paralysis. The mechanisms that trigger REM sleep paralysis are a matter of intense debate. Two competing theories argue that it is caused by either active inhibition or reduced excitation of somatic motoneuron activity. Here, we identify the transmitter and receptor mechanisms that function to silence skeletal muscles during REM sleep. We used behavioral, electrophysiological, receptor pharmacology and neuroanatomical approaches to determine how trigeminal motoneurons and masseter muscles are switched off during REM sleep in rats. We show that a powerful GABA and glycine drive triggers REM paralysis by switching off motoneuron activity. This drive inhibits motoneurons by targeting both metabotropic GABA(B) and ionotropic GABA(A)/glycine receptors. REM paralysis is only reversed when motoneurons are cut off from GABA(B), GABA(A) and glycine receptor-mediated inhibition. Neither metabotropic nor ionotropic receptor mechanisms alone are sufficient for generating REM paralysis. These results demonstrate that multiple receptor mechanisms trigger REM sleep paralysis. Breakdown in normal REM inhibition may underlie common sleep motor pathologies such as REM sleep behavior disorder.
authors: Department of Cell and Systems Biology, Systems Neurobiology Laboratory, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
authors: Patricia L
authors: PL
authors: Brooks
authors: John H
authors: JH
authors: Peever
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004576:Electromyography; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010291:Paresis / Q000378:metabolism / Q000503:physiopathology*; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D014278:Trigeminal Nuclei / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D018684:Glycine Agents; D010721:Phosphinic Acids; C083008:CGP 52432; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline