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

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

eLife (2018-11-14)
Ximena I Salinas-Hernández, Pascal Vogel, Sebastian Betz, Raffael Kalisch, Torfi Sigurdsson, Sevil Duvarci
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tyrosine Hydroxylase Antibody, clone LNC1, ascites fluid, clone LNC1, Chemicon®
Sigma-Aldrich
Anti-Tyrosine Hydroxylase Rabbit pAb, liquid, Calbiochem®