Redefining Noradrenergic Neuromodulation of Behavior: Impacts of a Modular Locus Coeruleus Architecture

Dan J. Chandler, Patricia Jensen, Jordan G. McCall, Anthony E. Pickering, Lindsay A. Schwarz, Nelson K. Totah

Research output: Contribution to journalArticle (Academic Journal)peer-review

104 Citations (Scopus)
151 Downloads (Pure)


The locus coeruleus (LC) is a seemingly singular and compact neuromodulatory nucleus that is a prominent component of disparate theories of brain function due to its broad noradrenergic projections throughout the CNS. As a diffuse neuromodulatory system, noradrenaline affects learning and decision making, control of sleep and wakefulness, sensory salience including pain, and the physiology of correlated forebrain activity (ensembles and networks) and brain hemodynamic responses. However, our understanding of the LC is undergoing a dramatic shift due to the application of state-of-the-art methods that reveal a nucleus of many modules that provide targeted neuromodulation. Here, we review the evidence supporting a modular LC based on multiple levels of observation (developmental, genetic, molecular, anatomical, and neurophysiological). We suggest that the concept of the LC as a singular nucleus and, alongside it, the role of the LC in diverse theories of brain function must be reconsidered.

Original languageEnglish
Pages (from-to)8239-8249
Number of pages11
JournalJournal of Neuroscience
Issue number42
Publication statusPublished - 16 Oct 2019

Structured keywords

  • Anaesthesia Pain and Critical Care


  • locus coeruleus
  • stress
  • pain
  • executive function
  • development


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