Adaptive gain and the role of the locus coeruleus-norepinephrine system in optimal performance

J Comp Neurol. 2005 Dec 5;493(1):99-110. doi: 10.1002/cne.20723.


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, anatomical, 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. 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. 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 prefrontal areas produce the above patterns of LC activity to optimize the utility of performance on both short and long time scales.

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.
  • Review

MeSH terms

  • Adaptation, Psychological / physiology*
  • Animals
  • Cerebral Cortex / physiology
  • Cognition / drug effects
  • Cognition / physiology
  • Dopamine / pharmacology
  • Dopamine / physiology
  • Learning / physiology
  • Locus Coeruleus / physiology*
  • Motor Activity
  • Norepinephrine / physiology*


  • Dopamine
  • Norepinephrine