Journal
ISCIENCE
Volume 26, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.105814
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Basal forebrain cholinergic neurons have an important role in associative learning and processing stimuli that predict future outcomes. This study used calcium imaging and spiking recordings to investigate the impact of outcome probabilities on these neurons in mice. The results showed that the cholinergic neurons responded more strongly to sensory cues that were often paired with reward, and reward delivery activated the neurons, with surprising rewards generating a stronger response. The findings suggest that the cholinergic neurons differentially weigh predictions of positive and negative reinforcement, reflecting the relative salience of appetitive and aversive outcomes.
Basal forebrain cholinergic neurons (BFCNs) play an important role in associative learning, suggesting that BFCNs may participate in processing stimuli that pre-dict 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, reflect-ing 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 expecta-tion-gated cholinergic firing is instructive to reward-seeking behaviors.
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