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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.
Highlights
The ability to learn which stimuli predict danger is crucial for survival but it is important to adapt behavior when those stimuli no longer represent a threat
Temporally specific optogenetic inhibition of DA neurons at the time of the unconditioned stimulus (US) omission prevented extinction, demonstrating that this signal is necessary for normal fear extinction
Enhancing this DA signal using temporally-specific optogenetic excitation was sufficient to accelerate extinction learning. These results identify a crucial role of DA neurons in signaling the unexpected omission of aversive outcomes and thereby driving fear extinction learning
Summary
The ability to learn which stimuli predict danger is crucial for survival but it is important to adapt behavior when those stimuli no longer represent a threat. Decades of research on fear extinction has revealed that a distributed network of brain structures including the amygdala, medial prefrontal cortex and hippocampus mediates the acquisition, consolidation and retrieval of fear extinction memories (Duvarci and Pare, 2014; Maren et al, 2013; Pape and Pare, 2010; SotresBayon and Quirk, 2010; Tovote et al, 2015). None of these structures have been shown to signal the absence of the expected aversive outcome during fear extinction. The neural substrates of such a signal that could initiate extinction learning have remained elusive
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