The proposed studies investigate factors influencing the development and maintenance of neural circuitry and functional responses in the central nervous system, and make use of the rodent primary visual pathway as a model system. Specifically, embryonic rat retinae will be transplanted to the dorsal midbrain surface of newborn host rats. The transplanted retinae will be allowed to mature, and the dynamics of the host's visual responses to transplant illumination will then be studied. The host optic projections will remain intact (unlike previous studies using this preparation), so that the transplant projection represents an anomalous alternate retinal input pathway which is present through most of the developmental stages and after maturation of the visual system. The functional effectiveness of transplanted retinae will be contrasted with that of the host eyes by quantifying pupillary light responses elicited by direct illumination. Quantification of this simple motor response to changing light levels will allow comparisons among transplant- elicited and normal pupillary responses in the same animals, before and after experimental manipulations and as a consequence of aging. Structural features of the transplanted and host retinae will then be evaluated histologically, and these structural findings correlated with those of the functional assays for individual animals. The general goal of these studies is to identify factors influencing functional responsiveness of the central nervous system to sensory stimuli, using neural transplants as tools to manipulate cell-cell interactions in the retina and among retinal inputs to central nuclei. Specific goals are 1) to evaluate the relative effectiveness of transplant and normal retinal inputs, and the potential for interaction among these inputs, 2) to evaluate the developmental influence of retinal pigment epithelial cells on retinal anatomy and function at maturity, 3) to determine if it is possible to enhance efficiency of retinal function by additional of RPE cells to mature transplanted retinae, and 4) to correlate structural and functional features contributing to optimal transplant efficiency as transplants age. The findings will be important for furthering an understanding of the capacity of an ectopic sensory input to influence normal behaviors, and factors contributing to this capacity during the developmental process and at maturity. The findings will also have implications for how behaviors based on multiple inputs may arise in the normal nervous system, and for how other behaviors may be influenced by different types of neural transplants. Finally, the proposed studies will provide an alternative model for considering the therapeutic potential of in oculo transplantation procedures, a perspective important for evaluating the anatomic and functional basis of such procedures prior to their widespread clinical application.
| Bone-Larson, C; Basu, S; Radel, J D et al. (2000) Partial rescue of the ocular retardation phenotype by genetic modifiers. J Neurobiol 42:232-47 |
