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

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  • EU Horizon2020 project DynaMORE (Dynamic MOdelling of REsilience)

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.
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... Several recent studies, including one from our group, report that dopaminergic neurons are activated in operant tasks and regulate taskrelated decision-making 4,7,41 . Emerging evidence also suggests that dopaminergic activity is triggered by and possibly regulates cueassociative aversive behavior 5,33,42 . We therefore examined dopaminergic activity in the auditory striatum and its possible role in auditory fear conditioning. ...
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... Furthermore, it is noteworthy that the mPFC extinction engram neurons also receive synaptic inputs from the mediodorsal nucleus of the thalamus (MD) and the ventral tegmental area (VTA). The MD is considered to play a regulatory role in fear extinction [89], while the VTA is implicated in the generation of bottom-up prediction error signals [90,91]. These inputs suggest that the formation of extinction memory engrams may involve the integration of multiple bottom-up signals by the mPFC engram neurons. ...
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