Dissecting Resting-State Plasticity: Mesoscale Calcium Imaging of Excitatory and Inhibitory Neuronal Population Network Reorganization in Early Blind Mice

Early sensory deprivation profoundly alters cortical organization, yet the cell-type–specific mechanisms driving large-scale functional reconfiguration remain poorly understood. Here, we combined wide-field mesoscale calcium imaging with cell-type–specific promoters (hSyn, Thy1, mDLX) to quantify resting-state functional connectivity across pan-neuronal, excitatory, and inhibitory networks in sighted and neonatal enucleated mice. Using graph-theoretic analyses of spontaneous cortical activity, we found that early visual deprivation induced a convergent pattern across neuronal populations in which medial higher visual and associative cortices strengthened connectivity with somatosensory and motor regions, while V1 and lateral higher visual areas lost network influence. However, reorganizations differed between neuronal population. Excitatory networks exhibited a reduced global efficiency and connection strength, revealing a selective vulnerability to sensory loss and a redistribution of hub architecture toward associative cortices. Global efficiency was preserved in the inhibitory network, but extensive hub reassignments and an increased cross-modular coupling were observed in this network, reflecting a reconfiguration of long-range inhibitory coordination. Pan-neuronal networks showed large-scale redistribution without global integration loss, suggesting a stabilized mesoscale balance between excitation and inhibition. Community detection revealed enhanced intermodular communication and population-specific reallocation of connectors, provincial, and bridging hubs. These results demonstrate that early blindness evokes a coordinated yet cell-type–specific reorganization of cortical mesoscale networks, in which excitatory and inhibitory populations contribute distinctively to cortical integration and plasticity. This population-resolved approach bridges mesoscale dynamics in mice with human evidence of occipital recruitment following sensory deprivation, offering mechanistic insight into the cellular foundations of cortical resilience and cross-modal plasticity.