Dopaminergic Activity Encodes and Modulates Freezing Behavior During Auditory Fear Extinction

Abstract

Striatal dopamine (DA) activity has long been implicated in encoding prediction errors in reward-based learning. However, the role of striatal DA in aversive learning remains largely unknown. We hypothesize that striatal DA encodes a teaching signal which enables extinction of an aversive association. To test this hypothesis, we use fiber photometry to record from striatal DA neurons during auditory fear conditioning. During conditioning, mice learn to associate a predictive cue (i.e. tone) to the coming of a foot shock, and consequently freeze upon the presentation of the tone. During extinction, mice hear the tone alone over multiple trials, and subsequently decrease freezing to the tone. We find that dopamine activity after tone offset in the nucleus accumbens (NAc) and dorsal medial striatum (DMS) encodes for current trial freezing and change in freezing. DA activity in NAc also encodes for next trial freezing. To see if cell body activation of VTA DA neurons reflects NAc terminal activity, we record from VTA DA neurons and find they have similar activity relative to NAc DA terminals. Together, these results provide evidence that dopamine activity at cue off is a teaching signal involved in extinction learning. To test for causality, we inhibited VTA DA neurons and saw increased freezing and slower extinction. This suggests the DA teaching signal is a prediction error (PE) that updates the tone-shock association and this is necessary for extinction. Understanding dopamine’s role during extinction of aversive stimuli can help better our understanding of psychiatric disorders like PTSD, which also involve an inability to extinguish aversive memories.