Cortical Functional Connectivity in Mouse Models of Early Blindness: Enucleation vs. Anophthalmia

Early sensory deprivation drives large-scale reconfiguration of cortical networks, yet we still lack a clear understanding of the relative contributions of early visual experience versus spontaneous prenatal retinal waves on the establishment of the cortical network. We compared two mouse models of congenital blindness: neonatal enucleation and congenital anophthalmia, across two genetic strains (C57Bl/6J and ZRDBA) using mesoscopic calcium imaging of spontaneous activity and graph-theoretical analysis. Spectral analyses revealed localized strain-specific increases in infraslow and low delta power following visual deprivation, with C57Bl/6J enucleated and ZRDBA anophthalmic mice exhibiting a more generalized nodal increase. Concomitantly, the functional network organization was redirected toward medial higher-order visual areas, the associative retrosplenial cortex, and somatosensory regions, while the primary and lateral visual cortices exhibited reduced influence and integration within the modular architecture. Notably, ZRDBA groups showed limited global changes to their cortical network. However, anophthalmic ZRDBA mice, lacking prenatal retinal waves, exhibited connectivity patterns more akin to enucleated C57Bl/6J than to their enucleated littermates, highlighting the instructive role of spontaneous prenatal retinal activity. These findings support a connectivity-constrained, experience-dependent model in which preexisting structural pathways guide diffuse, resilient reorganization following sensory loss.