Cholinergic activity reflects reward expectations and predicts behavioral responses.

Basal forebrain cholinergic neurons (BFCNs) play an important role in associative learning, suggesting that BFCNs may participate in processing stimuli that predict future outcomes. However, the impact of outcome probabilities on BFCN activity remained elusive. Therefore, we performed bulk calcium imaging and recorded spiking of identified cholinergic neurons from the basal forebrain of mice performing a probabilistic Pavlovian cued outcome task. BFCNs responded more to sensory cues that were often paired with reward. Reward delivery also activated BFCNs, with surprising rewards eliciting a stronger response, whereas punishments evoked uniform positive-going responses. We propose that BFCNs differentially weigh predictions of positive and negative reinforcement, reflecting divergent relative salience of forecasting appetitive and aversive outcomes, partially explained by a simple reinforcement learning model of a valence-weighed unsigned prediction error. Finally, the extent of cue-driven cholinergic activation predicted subsequent decision speed, suggesting that the expectation-gated cholinergic firing is instructive to reward-seeking behaviors.