title: Region-Specific Dissociation between Cortical Noradrenaline Levels and the Sleep/Wake Cycle.
abstract: OBJECTIVE
  The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking.
  
  
  METHODS
  We performed in vivo microdialysis experiments in adult (9-10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6).
  
  
  RESULTS
  We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC.
  
  
  CONCLUSIONS
  Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation.
  
  
  CONCLUSIONS
  A commentary on this article appears in this issue on page 11.
authors.affiliation: Dept. of Psychiatry, University of Wisconsin-Madison, Madison, WI.
authors.forename: Michele
authors.initials: M
authors.lastname: Bellesi
authors.affiliation: Dept. of Psychiatry, University of Wisconsin-Madison, Madison, WI.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.affiliation: Dept. of Psychiatry, University of Wisconsin-Madison, Madison, WI.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cirelli
authors.affiliation: Dept. of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Serra
mesh_terms: D000818:Animals; D004569:Electroencephalography; D008125:Locus Coeruleus / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism; D014851:Wakefulness / Q000502:physiology*
chemical_list: D009638:Norepinephrine
keywords: locus coeruleus; motor cortex; prefrontal cortex; sleep deprivation