Striatal Dopamine Represents Valence on Dynamic Regional Scales

Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict valenced stimuli, such as food or threat. Cue-guided behavior depends on a network of brain systems, including dopaminergic projections to the striatum. Critically, it remains unclear how dopamine signaling across the striatum encodes multi-valent, dynamic learning contexts, where positive and negative associations must be rapidly disambiguated. To understand this, we employed a Pavlovian discrimination paradigm, where cues predicting food or threat were intermingled during conditioning sessions, and their meaning was serially reversed across training. We found that male and female rats readily distinguished these cues and updated their behavior rapidly upon valence reversal. Using fiber photometry, we recorded dopamine signaling in three major striatal subregions - the dorsolateral striatum (DLS), the nucleus accumbens (NAc) core, and the nucleus accumbens medial shell - finding that valence was represented uniquely across all three regions, indicative of local signals biased for value and salience. Further, ambiguity introduced by cue reversals reshaped striatal dopamine on different timelines: nucleus accumbens signals updated more readily than those in the DLS. Together, these results indicate that striatal dopamine flexibly encodes stimulus valence according to region-specific rules, and these signals are dynamically modulated by changing contingencies in the resolution of ambiguity about the meaning of environmental cues.<b>Significance Statement</b> Adaptive decision making relies on updating learned associations to disambiguate predictions of reward or threat. This cue-guided behavior depends on striatal dopamine, but it remains unclear how dopamine signaling encodes multi-valent, dynamic learning contexts. Here, we employed a paradigm where cues predicting positive and negative outcomes were intermingled, and their meaning was serially reversed across time. We recorded dopamine signaling, finding heterogeneous patterns of valence encoding across striatal subregions, and cue reversal reshaped subregional signals on different timelines. Our results suggest that dopamine flexibly encodes dynamic learning contexts to resolve ambiguity about the meaning of environmental cues.