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

  1. Ximena I Salinas-Hernández
  2. Pascal Vogel
  3. Sebastian Betz
  4. Raffael Kalisch
  5. Torfi Sigurdsson
  6. Sevil Duvarci  Is a corresponding author
  1. Goethe University Frankfurt, Germany
  2. Johannes Gutenberg University, Germany
Research Article
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Cite this article as: eLife 2018;7:e38818 doi: 10.7554/eLife.38818

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Ximena I Salinas-Hernández

    Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Pascal Vogel

    Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sebastian Betz

    Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Raffael Kalisch

    Neuroimaging Center, Johannes Gutenberg University, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Torfi Sigurdsson

    Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Sevil Duvarci

    Institute of Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    For correspondence
    duvarci@med.uni-frankfurt.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4494-7741

Funding

Deutsche Forschungsgemeinschaft (SFB1193 Grant INST247/852-1)

  • Sevil Duvarci

Deutsche Forschungsgemeinschaft (SFB1193 Grant INST247/854-1)

  • Torfi Sigurdsson

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

Ethics

Animal experimentation: All procedures were conducted in accordance with the guidelines of the German Animal Protection Act and were approved by the local authorities (Regierungsprasidium Darmstadt; protocol number 1038). Every effort was made to minimize suffering.

Reviewing Editor

  1. Rui M Costa, Columbia University in the City of New York, United States

Publication history

  1. Received: June 5, 2018
  2. Accepted: November 8, 2018
  3. Accepted Manuscript published: November 13, 2018 (version 1)
  4. Version of Record published: November 27, 2018 (version 2)

Copyright

© 2018, Salinas-Hernández et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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