A dopaminergic switch for fear to safety transitions

Nat Commun. 2018 Jun 27;9(1):2483. doi: 10.1038/s41467-018-04784-7.


Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioral roles for different dopamine neuron projections in fear extinction learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Classical
  • Dopamine / metabolism
  • Dopaminergic Neurons / physiology*
  • Electric Stimulation
  • Electrodes
  • Fear*
  • Male
  • Models, Animal
  • Neural Pathways
  • Nucleus Accumbens / physiology*
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Long-Evans
  • Reward
  • Ventral Tegmental Area / physiology*


  • Dopamine