Accumbal acetylcholine signals associative salience during learning

Abstract Learning is driven by prediction errors, which determine what is learned, and salience, which controls the learning rate. Dopamine in the nucleus accumbens correlates with prediction errors, but salience mechanisms are less clear. We hypothesized that acetylcholine acts as a salience signal, as it regulates dopamine-induced plasticity. To test this, we recorded acetylcholine and dopamine dynamics in rats across three learning tasks. Our findings reveal a characteristic pattern of evolving neuromodulator responses during learning. First, indiscriminate cholinergic dips appeared, then dopamine responses differentiated based on predicted value, followed by the cholinergic dips also varying by value. Stable performance required this full pattern, and acetylcholine dips could be decoupled from value by changing reward contingencies. The observed acetylcholine dynamics fit an associative salience term predicted by hybrid attentional associative learning models, suggesting that dopamine and acetylcholine act complementarily to determine the content and rate of learning. Teaser Acetylcholine shapes learning rate by signaling the salience of predictive cues.