Cortical reactivations of recent sensory experiences predict bidirectional network changes during learning

Salient experiences are often relived in the mind. Human neuroimaging studies suggest that such experiences drive activity patterns in visual association cortex that are subsequently reactivated during quiet waking. Yet, the circuit-level consequences of such reactivations remain unclear. Here, we imaged hundreds of neurons in visual association cortex across days as mice learned a visual discrimination task. Distinct patterns of neurons were activated by different visual cues. These same patterns were subsequently reactivated during quiet waking in darkness, with higher reactivation rates during early learning and for food-predicting vs. neutral cues. Reactivations involving ensembles of neurons encoding both the food cue and the reward predicted strengthening of next-day functional connectivity of participating neurons, while the converse was observed for reactivations involving ensembles encoding only the food cue. We propose that task-relevant neurons strengthen, while task-irrelevant neurons weaken their dialogue with the network via participation in distinct flavors of reactivation.