Differential modulation of aversive signaling by expectation across the cingulate cortex

Pain-related aversion is an affective-motivational state driven by sensory experience that promotes learning and recruits widespread cortical networks, yet how distinct cingulate subregions contribute to its adaptive utility remains poorly understood. Here we used longitudinal one-photon calcium imaging in mice to compare dynamics in the anterior cingulate cortex (ACC) and retrosplenial cortex (RSC) across repeated unsignaled foot-shocks and fear conditioning and extinction paradigm. Both regions contained relatively stable ensembles that responded robustly to shocks, indicating shared encoding of acute nociceptive events. However, only the RSC flexibly reorganized its population activity when shocks were preceded by predictive cues. These anticipatory dynamics in the RSC predicted the rate of fear learning across individuals and subsequent extinction. By contrast, the ACC maintained shock-responsive ensembles with limited cue modulation. Instead, its dynamics encoded decisions to freeze, aligning with its role in encoding ongoing nociception and driving immediate defensive behavior. Together, these results reveal a division of labor in which the ACC emphasizes ongoing nociceptive processing, while the RSC transforms sensory signals into predictive codes that shape learning and memory. This specialization highlights how distributed cortical computations cooperate to generate the adaptive value of aversion. More broadly, our findings suggest that these regions assume complementary roles to address immediate sensory-motivational responses while flexibly reconfiguring to support long-term behavioral adaptation.