An endogenous glutamatergic drive onto somatic motoneurons contributes to the stereotypical pattern of muscle tone across the sleep-wake cycle

J Neurosci. 2008 Apr 30;28(18):4649-60. doi: 10.1523/JNEUROSCI.0334-08.2008.


Skeletal muscle tone is modulated in a stereotypical pattern across the sleep-wake cycle. Abnormalities in this modulation contribute to most of the major sleep disorders; therefore, characterizing the neurochemical substrate responsible for transmitting a sleep-wake drive to somatic motoneurons needs to be determined. Glutamate is an excitatory neurotransmitter that modulates motoneuron excitability; however, its role in regulating motoneuron excitability and muscle tone during natural sleep-wake behaviors is unknown. Therefore, we used reverse-microdialysis, electrophysiology, pharmacological, and histological methods to determine how changes in glutamatergic neurotransmission within the trigeminal motor pool contribute to the sleep-wake pattern of masseter muscle tone in behaving rats. We found that blockade of non-NMDA and NMDA glutamate receptors (via CNQX and d-AP-5) on trigeminal motoneurons reduced waking masseter tone to sleeping levels, indicating that masseter tone is maximal during alert waking because motoneurons are activated by an endogenous glutamatergic drive. This wake-related drive is switched off in non-rapid eye movement (NREM) sleep, and this contributes to the suppression of muscle tone during this state. We also show that a functional glutamatergic drive generates the muscle twitches that characterize phasic rapid-eye movement (REM) sleep. However, loss of a waking glutamatergic drive is not sufficient for triggering the motor atonia that characterizes REM sleep because potent activation of either AMPA or NMDA receptors on trigeminal motoneurons was unable to reverse REM atonia. We conclude that an endogenous glutamatergic drive onto somatic motoneurons contributes to the stereotypical pattern of muscle tone during wakefulness, NREM sleep, and phasic REM sleep but not during tonic REM sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Electroencephalography
  • Electromyography
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Male
  • Masseter Muscle / physiology
  • Microdialysis / methods
  • Motor Neurons / metabolism*
  • Muscle Tonus / drug effects
  • Muscle Tonus / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sleep* / drug effects
  • Spectrum Analysis / methods
  • Trigeminal Nuclei / cytology*
  • Wakefulness* / drug effects


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione