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 speci...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/38818 |
| _version_ | 1828380096025591808 |
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| author | Ximena I Salinas-Hernández Pascal Vogel Sebastian Betz Raffael Kalisch Torfi Sigurdsson Sevil Duvarci |
| author_facet | Ximena I Salinas-Hernández Pascal Vogel Sebastian Betz Raffael Kalisch Torfi Sigurdsson Sevil Duvarci |
| author_sort | Ximena I Salinas-Hernández |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:51:26Z |
| format | Article |
| id | doaj.art-6d181a001b164d1e800aac98c03acdce |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:51:26Z |
| publishDate | 2018-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6d181a001b164d1e800aac98c03acdce2022-12-22T02:03:14ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.38818Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomesXimena I Salinas-Hernández0Pascal Vogel1Sebastian Betz2Raffael Kalisch3Torfi Sigurdsson4Sevil Duvarci5https://orcid.org/0000-0003-4494-7741Institute of Neurophysiology, Neuroscience Center, Goethe University, Frankfurt, GermanyInstitute of Neurophysiology, Neuroscience Center, Goethe University, Frankfurt, GermanyInstitute of Neurophysiology, Neuroscience Center, Goethe University, Frankfurt, GermanyDeutsches Resilienz Zentrum, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Neuroimaging Center, Focus Program Translational Neuroscience, Johannes Gutenberg University, Mainz, GermanyInstitute of Neurophysiology, Neuroscience Center, Goethe University, Frankfurt, GermanyInstitute of Neurophysiology, Neuroscience Center, Goethe University, Frankfurt, GermanyExtinction 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.https://elifesciences.org/articles/38818dopaminefear conditioningextinctionsafety learning |
| spellingShingle | Ximena I Salinas-Hernández Pascal Vogel Sebastian Betz Raffael Kalisch Torfi Sigurdsson Sevil Duvarci Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes eLife dopamine fear conditioning extinction safety learning |
| title | Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| title_full | Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| title_fullStr | Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| title_full_unstemmed | Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| title_short | Dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| title_sort | dopamine neurons drive fear extinction learning by signaling the omission of expected aversive outcomes |
| topic | dopamine fear conditioning extinction safety learning |
| url | https://elifesciences.org/articles/38818 |
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