Anterior cingulate cortex in complex associative learning: monitoring action state and action content

Abstract Environmental changes necessitate adaptive responses, and thus the ability to monitor one’s actions and their connection to specific cues and outcomes is crucial for survival. The anterior cingulate cortex (ACC) is implicated in these processes, yet its precise role in action monitoring versus outcome tracking remains unclear. To investigate this, we developed a novel discrimination–avoidance task for mice, designed with clear temporal separation between actions and outcomes. Our findings show that ACC neurons primarily encode post-action variables over extended periods, reflecting the animal’s preceding actions rather than the outcomes or values of those actions. Specifically, we identified two distinct subpopulations of ACC neurons: one encoding the action state (whether an action was taken) and the other encoding the action content (which action was taken). Importantly, increased post-action ACC activity was associated with better performance in subsequent trials. These findings suggest that the ACC supports complex associative learning through extended signaling of rich action-relevant information, thereby bridging cue, action, and outcome associations. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵† Co-first authors Two additional supplementary figures have been added.