Excitatory and Inhibitory Networks Diverge Following Early Blindness

Abstract

Early visual deprivation profoundly reshapes cortical functional organization, yet the contribution of distinct neuronal populations to large-scale network plasticity remains unclear. We combined awake wide-field mesoscale calcium imaging withing promoter-defined neuronal populations to characterize resting-state functional connectivity in pan-neuronal (hSyn), excitatory (Thy1), and inhibitory (mDLX) cortical networks in sighted and neonatal enucleated mice. Graph-theoretical analyses revealed a convergent reorganization pattern across populations in which medial higher visual and associative cortices strengthened their connectivity with somatosensory and motor regions, whereas primary visual cortex and lateral higher visual areas lost network influence. Despite this shared motif, network remodeling differed according to neuronal identity. Excitatory networks exhibited pronounced redistribution of nodal influence and modular organization with selective alterations of global network topology, indicating selective susceptibility to sensory deprivation. Inhibitory networks preserved global efficiency while showing localized reorganization of connector and bridging hubs. Pan-neuronal networks displayed extensive redistribution of connectivity and hub architecture despite relatively preserved global network organization. These findings demonstrate that early blindness induces coordinated yet neuronal identity-dependent mesoscale network plasticity, linking mouse cortical dynamics with systems-level evidence of cross-modal reorganization in blind individuals.