An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance

Annu Rev Neurosci. 2005;28:403-50. doi: 10.1146/annurev.neuro.28.061604.135709.


Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Adaptation, Physiological / physiology*
  • Animals
  • Brain Mapping
  • Cognition / physiology
  • Humans
  • Locus Coeruleus / physiology*
  • Neural Networks, Computer
  • Norepinephrine / physiology*
  • Systems Integration*
  • Time Factors


  • Norepinephrine