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

  • 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.

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Author:Ximena I. Salinas-Hernández, Pascal Vogel, Sebastian Betz, Raffael Kalisch, Torfi SigurdssonORCiD, Sevil Duvarci
URN:urn:nbn:de:hebis:30:3-489906
DOI:https://doi.org/10.7554/eLife.38818
ISSN:2050-084X
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30421719
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Place of publication:Cambridge
Contributor(s):Rui M. Costa
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/11/13
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/14
Tag:Dopamine; Extinction; Fear conditioning; Mouse; Neuroscience; Research article; Safety learning
Volume:7
Issue:e38818
Page Number:25
First Page:1
Last Page:25
Note:
Copyright Salinas-Hernández et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
HeBIS-PPN:448053241
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0