VISION LOSS TRIGGERS TRANSIENT CHANGES IN MOTOR-RELATED CORTICAL STATES IN THE ADULT MOUSE VISUAL CORTEX

Loss of visual input in adulthood profoundly reshapes cortical function, yet the dynamics of this adaptation remain elusive. Homeostatic plasticity mechanisms are known to restore excitatory activity levels in the primary visual cortex (V1) within a few days, but how activity evolves beyond that timescale is unknown. Using longitudinal mesoscopic calcium imaging across the dorsal cortex of adult mice, we tracked large-scale activity before and after bilateral enucleation (BE) during head-fixed spontaneous behaviour. We reveal that BE not only alters V1 activity but also disrupts its modulation by behavioural state—a fundamental organising principle of cortical processing. Strikingly, locomotion-driven enhancement of V1 activity collapsed within 24 hours, while quiescent periods became dominated by slow oscillations within 1 week. These opposing, state-dependent changes followed distinct recovery trajectories, converging only at ~10 weeks. Thus, beyond the rapid homeostatic stabilisation of excitatory activity, the restoration of behavioural-state modulation of large-scale cortical dynamics unfolds over a much longer timescale. This could reflect slow rewiring of cortical circuitry, temporarily disrupting basic functions to achieve long-term stability. This study describes long-term changes in activity following an abrupt decrease in cortical excitation, but the underlying mechanisms remain unknown. Further research into this ten-week window will deepen our understanding of the brain’s ability to adapt.