Cortical reactivations predict future sensory responses

How do we learn about experiences while being removed from the experience itself? One solution involves offline learning via reactivations. Sensory reactivation involves the recurrence of a pattern of neural activity during sleep or quiet waking that previously occurred during a sensory experience. Prevailing theories of offline memory consolidation posit that the pattern of neurons activated during a sensory experience will be faithfully reactivated, thereby stabilizing the entire pattern. However, sensory-evoked patterns are not stable, but instead drift across repeated experiences. Our study investigates potential roles of reactivations in the stabilization and/or drift of sensory representations. We performed two-photon calcium imaging from ~6,600 neurons simultaneously in lateral visual cortex as mice passively viewed two distinct visual stimuli for hours each day. Each stimulus presentation was followed by a one-minute inter-trial interval to assess for stimulus reactivations. Presentation of a stimulus resulted in transient, stimulus-specific reactivations during the following minute. Stimulus reactivation rates decreased across time, and strongly reflected the content of the most recently presented stimulus. These reactivations depended on local circuit activity, as they were abolished by local silencing during the preceding stimulus. Contrary to prevailing theories, reactivations systemically differed from previous patterns evoked by the stimulus. Instead, they were more similar to future patterns evoked by the stimulus, thereby predicting representational drift. In particular, neurons that participated more or less in early reactivations than in stimulus response patterns subsequently increased or decreased their future stimulus responses, respectively. Using a simple plasticity model, we found that the rate and content of these reactivations was sufficient to accurately predict future changes in stimulus responses and, surprisingly, the decreasing similarity of responses to distinct stimuli. Thus, activity patterns during sensory cortical reactivations may guide the drift in sensory responses to improve sensory discrimination.