PT - JOURNAL ARTICLE AU - Masashi Kondo AU - Masanori Matsuzaki TI - Independent representations of reward-predicting cues and reward history in frontal cortical neurons AID - 10.1101/2020.01.23.916460 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.23.916460 4099 - http://biorxiv.org/content/early/2020/01/24/2020.01.23.916460.short 4100 - http://biorxiv.org/content/early/2020/01/24/2020.01.23.916460.full AB - The transformation of sensory inputs to appropriate goal-directed actions requires estimation of sensory-cue values based on outcome history. To clarify how cortical neurons represent an outcome-predicting cue and actual outcome, we conducted wide-field and two-photon calcium imaging of the mouse neocortex during performance of a classical conditioning task with two cues with different water-reward probabilities. Although licking behavior dominated the area-averaged activity over the whole dorsal neocortex, dorsomedial frontal cortex (dmFrC) affected other dorsal frontal cortical activities, and its inhibition extinguished differences in anticipatory licking between the cues. In individual frontal cortical neurons, the reward-predicting cue was not simultaneously represented with the current or past reward, but licking behavior was frequently multiplexed with the reward-predicting cue and current or past reward. Deep-layer neurons in dmFrC most strongly represented the reward-predicting cue and recent reward history. Our results suggest that these neurons ignite the cortical processes required to select appropriate actions.