Phasic dopamine release in the medial prefrontal cortex enhances stimulus discrimination

Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3169-76. doi: 10.1073/pnas.1606098113. Epub 2016 May 16.

Abstract

Phasic dopamine (DA) release is believed to guide associative learning. Most studies have focused on projections from the ventral tegmental area (VTA) to the striatum, and the action of DA in other VTA target regions remains unclear. Using optogenetic activation of VTA projections, we examined DA function in the medial prefrontal cortex (mPFC). We found that mice perceived optogenetically induced DA release in mPFC as neither rewarding nor aversive, and did not change their previously learned behavior in response to DA transients. However, repetitive temporal pairing of an auditory conditioned stimulus (CS) with mPFC DA release resulted in faster learning of a subsequent task involving discrimination of the same CS against unpaired stimuli. Similar results were obtained using both appetitive and aversive unconditioned stimuli, supporting the notion that DA transients in mPFC do not represent valence. Using extracellular recordings, we found that CS-DA pairings increased firing of mPFC neurons in response to CSs, and administration of D1 or D2 DA-receptor antagonists in mPFC during learning impaired stimulus discrimination. We conclude that DA transients tune mPFC neurons for the recognition of behaviorally relevant events during learning.

Keywords: attention; dopamine; learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Action Potentials
  • Animals
  • Auditory Pathways*
  • Benzazepines / pharmacology
  • Conditioning, Psychological
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology*
  • Discrimination Learning / radiation effects
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Light*
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / radiation effects
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D2 / chemistry
  • Stimulation, Chemical
  • Sulpiride / pharmacology

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • SCH 23390
  • Sulpiride
  • Dopamine