Accumbal acetylcholine signals associative salience

Learning in dynamic environments requires animals to not only associate cues with outcomes but also to determine cue salience, which modulates how quickly related associations are updated. While dopamine (DA) in the nucleus accumbens core (NAcc) has been implicated in learning associations, the mechanisms of salience are less understood. Here, we tested the hypothesis that acetylcholine (ACh) in the NAcc encodes cue salience. We conducted four odor discrimination experiments in rats while simultaneously measuring accumbal ACh and DA. We found that ACh developed characteristic dips to cues over learning before DA signals differentiated cues by value, with these dips persisting through value decreases and developing faster during meta-learning. The dips reflected the cue salience across learning stages and tasks, as predicted by a hybrid attentional associative learning model that integrated principles from the Mackintosh and Pearce-Hall models, suggesting that accumbal ACh signals encode salience and potentially gate the learning process.