Cholinergic activity reflects reward expectations and predicts behavioral responses

Area of Science:

• Neuroscience
• Behavioral Neuroscience

Background:

• Basal forebrain cholinergic neurons (BFCNs) are vital for associative learning.
• Their role in processing stimuli predicting future outcomes is established, but the influence of outcome probabilities on BFCN activity was unclear.

Purpose of the Study:

• To investigate how outcome probabilities affect BFCN activity during a probabilistic Pavlovian cued outcome task.
• To explore the role of BFCNs in predicting and responding to appetitive and aversive outcomes.

Main Methods:

• Bulk calcium imaging and single-unit electrophysiological recordings were used in mice.
• Identified cholinergic neurons in the basal forebrain were monitored during a probabilistic Pavlovian task.

Main Results:

• BFCNs showed increased responses to sensory cues frequently paired with rewards.
• Reward delivery activated BFCNs, with unexpected rewards yielding stronger responses; punishments elicited uniform positive responses.
• A reinforcement learning model incorporating valence-weighted unsigned prediction error partially explained BFCN responses.

Conclusions:

• BFCNs differentially weigh predictions of positive and negative reinforcement, indicating distinct salience for appetitive and aversive outcome forecasting.
• Cue-induced cholinergic activation predicted decision speed, suggesting expectation-gated cholinergic firing guides reward-seeking behaviors.