Early blindness results in abnormal corticocortical and thalamocortical connections.

Studies in congenitally blind and bilaterally enucleated individuals show that an early loss of sensory driven activity can lead to massive functional reorganization. However, the anatomical substrate for this functional reorganization is unknown. In the present study, we examined patterns of corticocortical and thalamocortical connections in adult opossums that had been bilaterally enucleated neonatally, prior to the formation of retinogeniculate and geniculocortical connections. We show that in addition to normal thalamocortical projection patterns from visual nuclei, enucleated animals also receive input from nuclei associated with the somatosensory (ventral posterior nucleus, VP), auditory (medial geniculate nucleus, MGN), motor (ventrolateral nucleus, VL), and limbic/hippocampal systems (anterior dorsal nucleus, AD; and anterior ventral nucleus, AV). Likewise, in addition to normal corticocortical projections to area 17, bilaterally enucleated opossums also receive input from auditory, somatosensory, and multimodal cortex. These aberrant patterns of thalamocortical and corticocortical connections can account for alterations in functional organization observed in the visual cortex of bilateral enucleated animals, and indicate that factors extrinsic to the cortex play a large role in cortical field development and evolution. On the other hand, the maintenance of normal patterns of connections in the absence of visual input suggests that there are formidable constraints imposed on the developing cortex that highly restrict the types of evolutionary change possible.

Formation of cortical fields on a reduced cortical sheet.

Theories of both cortical field development and cortical evolution propose that thalamocortical projections play a critical role in the differentiation of cortical fields (; ). In the present study, we examined how changing the size of the immature neocortex before the establishment of thalamocortical connections affects the subsequent development and organization of the adult neocortex. This alteration in cortex is consistent with one of the most profound changes made to the mammalian neocortex throughout evolution: cortical size. Removing the caudal one-third to three-fourths of the cortical neuroepithelial sheet unilaterally at an early stage of development in marsupials resulted in normal spatial relationships between visual, somatosensory, and auditory cortical fields on the remaining cortical sheet. Injections of neuroanatomical tracers into the reduced cortex revealed in an altered distribution of thalamocortical axons; this alteration allowed the maintenance of their original anteroposterior distribution. These results demonstrate the capacity of the cortical neuroepithelium to accommodate different cortical fields at early stages of development, although the anteroposterior and mediolateral relationships between cortical fields appear to be invariant. The shifting of afferents and efferents with cortical reduction or expansion at very early stages of development may have occurred naturally in different lineages over time and may be sufficient to explain much of the phenotypic variation in cortical field number and organization in different mammals.