Neurochemical Research

, Volume 37, Issue 11, pp 2496–2512 | Cite as

Norepinephrine: A Neuromodulator That Boosts the Function of Multiple Cell Types to Optimize CNS Performance

  • John O’Donnell
  • Douglas Zeppenfeld
  • Evan McConnell
  • Salvador Pena
  • Maiken NedergaardEmail author


Norepinephrine (NE) is a neuromodulator that in multiple ways regulates the activity of neuronal and non-neuronal cells. NE participates in the rapid modulation of cortical circuits and cellular energy metabolism, and on a slower time scale in neuroplasticity and inflammation. Of the multiple sources of NE in the brain, the locus coeruleus (LC) plays a major role in noradrenergic signaling. Processes from the LC primarily release NE over widespread brain regions via non-junctional varicosities. We here review the actions of NE in astrocytes, microglial cells, and neurons based on the idea that the overarching effect of signaling from the LC is to maximize brain power, which is accomplished via an orchestrated cellular response involving most, if not all cell types in CNS.


Astrocyte Microglia Glycogen Potassium Inflammation Synaptic scaling 



This study was supported by funding from NIH/NINDS (NS075177 and NS078304), the W. M. Keck Foundation, and the Dana Foundation. We thank Leif Hertz for comments on the manuscript.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • John O’Donnell
    • 1
  • Douglas Zeppenfeld
    • 1
  • Evan McConnell
    • 1
  • Salvador Pena
    • 1
  • Maiken Nedergaard
    • 1
    Email author
  1. 1.Division of Glial Disease and Therapeutics, Center for Translational NeuromedicineUniversity of RochesterRochesterUSA

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