title: A noradrenergic mechanism functions to couple motor behavior with arousal state.
abstract: BACKGROUND
  Appropriate levels of skeletal muscle tone are needed to support routine motor behaviors. But, the brain mechanisms that function to couple muscle tone with waking behaviors are unknown. We addressed this question by studying mice with cataplexy--a condition caused by a decoupling of motor and arousal behaviors. Cataplexy is characterized by involuntary loss of muscle tone during wakefulness, which results in postural collapse during otherwise normal consciousness. Cataplexy is caused by loss of hypocretin (orexin) cells, but it is unknown how this loss triggers motor inactivity during cataplexy. Here, we used hypocretin knockout mice to identify the neurochemical cause of cataplexy and to determine the biochemical mechanisms that normally function to couple arousal and motor systems.
  
  
  RESULTS
  Using genetic, behavioral, electrophysiological, and pharmacological approaches, we show that the noradrenergic system acts to synchronize motor and arousal systems. Specifically, we show that an excitatory noradrenergic drive maintains postural muscle tone during wakefulness by activating α1 receptors on skeletal motoneurons. Loss of this normal excitatory drive triggers motor inactivity during cataplexy by reducing motoneuron excitation. However, loss of this drive does not affect arousal since mice remain awake during cataplexy, suggesting the noradrenergic system is not required for maintaining wakefulness. Artificial restoration of noradrenergic drive to motoneurons prevents motor inactivity and rescues cataplexy.
  
  
  CONCLUSIONS
  We conclude that hypocretin deficiency causes cataplexy by short-circuiting the noradrenergic drive to skeletal motoneurons. We suggest that the noradrenergic system functions to couple the brain systems that control postural muscle tone and behavioral arousal state.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, M5S 3G5, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Burgess
authors.forename: John H
authors.initials: JH
authors.lastname: Peever
mesh_terms: D000818:Animals; D002385:Cataplexy / Q000503:physiopathology*; D004569:Electroencephalography; D004594:Electrophysiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics; D000068797:Orexins; D011941:Receptors, Adrenergic / Q000502:physiology; D012890:Sleep / Q000502:physiology; D014851:Wakefulness / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011941:Receptors, Adrenergic