Dopamine tunes prefrontal outputs to orchestrate aversive processing

Brain Res. 2019 Jun 15:1713:16-31. doi: 10.1016/j.brainres.2018.11.044. Epub 2018 Dec 1.


Decades of research suggest that the mesocortical dopamine system exerts powerful control over mPFC physiology and function. Indeed, dopamine signaling in the medial prefrontal cortex (mPFC) is implicated in a vast array of processes, including working memory, stimulus discrimination, stress responses, and emotional and behavioral control. Consequently, even slight perturbations within this delicate system result in profound disruptions of mPFC-mediated processes. Many neuropsychiatric disorders are associated with dysregulation of mesocortical dopamine, including schizophrenia, depression, attention deficit hyperactivity disorder, post-traumatic stress disorder, among others. Here, we review the anatomy and functions of the mesocortical dopamine system. In contrast to the canonical role of striatal dopamine in reward-related functions, recent work has revealed that mesocortical dopamine fine-tunes distinct efferent projection populations in a manner that biases subsequent behavior towards responding to stimuli associated with potentially aversive outcomes. We propose a framework wherein dopamine can serve as a signal for switching mPFC states by orchestrating how information is routed to the rest of the brain.

Keywords: Aversion; Mesocortical; Mesolimbic; Signal-to-noise ratio; Valence.

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

  • Animals
  • Brain
  • Corpus Striatum / physiology
  • Dopamine / metabolism*
  • Dopamine / pharmacology*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology
  • Emotions
  • Humans
  • Neurons
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiology
  • Reward
  • Ventral Tegmental Area / physiology


  • Dopamine