Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes

Elife. 2018 Nov 13:7:e38818. doi: 10.7554/eLife.38818.


Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning.

Keywords: dopamine; extinction; fear conditioning; mouse; neuroscience; safety learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning*
  • Dopaminergic Neurons / physiology*
  • Electroencephalography
  • Extinction, Psychological*
  • Fear*
  • Learning*
  • Male
  • Mice, Inbred C57BL
  • Optogenetics
  • Photometry
  • Ventral Tegmental Area / physiology*

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.