Bilateral enucleation alters gene expression and intraneocortical connections in the mouse

BACKGROUND: Anatomically and functionally distinct sensory and motor neocortical areas form during mammalian development through a process called arealization. This process is believed to be reliant on both activity-dependent and activity-independent mechanisms. Although both mechanisms are thought to function concurrently during arealization, the nature of their interaction is not understood. To examine the potential interplay of extrinsic activity-dependent mechanisms, such as sensory input, and intrinsic activity-independent mechanisms, including gene expression in mouse neocortical development, we performed bilateral enucleations in newborn mice and conducted anatomical and molecular analyses 10 days later. In this study, by surgically removing the eyes of the newborn mouse, we examined whether early enucleation would impact normal gene expression and the development of basic anatomical features such as intraneocortical connections and cortical area boundaries in the first 10 days of life, before natural eye opening. We examined the acute effects of bilateral enucleation on the lateral geniculate nucleus of the thalamus and the neocortical somatosensory-visual area boundary through detailed analyses of intraneocortical connections and gene expression of six developmentally regulated genes at postnatal day 10. RESULTS: Our results demonstrate short-term plasticity on postnatal day 10 resulting from the removal of the eyes at birth, with changes in nuclear size and gene expression within the lateral geniculate nucleus as well as a shift in intraneocortical connections and ephrin A5 expression at the somatosensory-visual boundary. In this report, we highlight the correlation between positional shifts in ephrin A5 expression and improper refinement of intraneocortical connections observed at the somatosensory-visual boundary in enucleates on postnatal day 10. CONCLUSIONS: Bilateral enucleation induces a positional shift of both ephrin A5 expression and intraneocortical projections at the somatosensory-visual border in only 10 days. These changes occur prior to natural eye opening, suggesting a possible role of spontaneous retinal activity in area border formation within the neocortex. Through these analyses, we gain a deeper understanding of how extrinsic activity-dependent mechanisms, particularly input from sensory organs, are integrated with intrinsic activity-independent mechanisms to regulate neocortical arealization and plasticity.