Loss of Postnatal Retinal Input Perturbs Cortical Lamination in the Developing Ferret Visual Cortex

Neuroanatomical development of the visual system is influenced by activity-dependent processes. Removal of retinal input early in development in animal model experiments reproduces several structural characteristics of the primary visual cortex in humans who have been blinded early in life. Yet, many questions regarding how the loss of retinal activity affects the organization and cellular composition of the visual cortex remain to be answered. Here, we report alterations to primary visual cortex development in ferrets over the postnatal day 20 (P20) to P38 age range that arise following bilateral enucleation on P7. Most notably, during this age range, V1 is observed to become thicker in P7 enucleates than in control animals. While this effect recapitulates observations of abnormally thick visual cortex in early blind humans, the observation that the thickness difference is observable by P32, while the cortex is still developing, has implications that run counter to prevailing interpretations of the V1 thickness difference. In order to further characterize the cytoarchitectural development of V1, we quantify the number and distribution of the two largest populations of inhibitory neurons through postnatal development, illustrating how the emergence of visual input-dependent organization displays a unique time course in both controls and enucleates. We observe perturbations to macroscopic anatomical development with only minor effects on the number and distribution of interneurons present throughout late corticogenesis following binocular enucleation. Our results demonstrate that postnatal enucleation can produce substantial and durable alterations to the mature organization of the visual cortex, likely mirroring those occurring in human patients who lose sight early in life. Our findings identify specific cellular and molecular alterations and highlight challenges that will need to be addressed in the design and development of restorative therapeutics.