Temporal Dynamics of Cortical State Plasticity Following Adult Vision Loss

The adult brain retains a capacity for adaptation, yet the long-term sequence of plasticity remains poorly understood. To address this, we performed longitudinal mesoscopic calcium imaging of the dorsal cortex in spontaneously behaving adult mice before and after bilateral enucleation (BE). We uncovered behaviour-dependent and spatially distinct changes in cortical activity organised into two sequential, overlapping windows. An early window, spanning from day 1 to week 3–5, was marked by reduced activity in visual and retrosplenial cortices during locomotion, with movements suppressing rather than enhancing activity, as is typically observed. A second, delayed window (week 1 to week 7–10, peaking around 3 weeks) was characterised by increased slow-wave activity in primary visual cortex (V1) and lateromedial visual area (LM), indicative of heightened excitability. Consistently, activity increased—rather than decreased—at the transition from locomotion to quiescence. In parallel, we observed a rapid, long-lasting, and behaviour-dependent reorganisation of cortical network structure. Together, these findings demonstrate that cortical states in the adult brain are dynamic and can undergo substantial, months-long plasticity. The temporal and spatial dissociations between windows identified suggest distinct plasticity mechanisms in the circuit regulating cortical states. Therefore, our study provides a spatiotemporal framework to guide future investigations into the mechanisms of plasticity in the mature brain.