The proposed work continues an investigation using embryonic retinal transplantation techniques in rodents to examine how functioning neural circuits, that form the substrates for vision, develop and can be modified in maturity. The connections made by retinal grafts will be examined in detail and correlated with functional responses. These responses will be recorded both physiologically and behaviorally (using the pupillary reflex and a conditioned suppression paradigm). Besides defining the optimal conditions for graft function, we plan to use the preparations for examining sprouting of graft connections after injury to the adult host visual system. Five interrelated studies are proposed. The first will examine the substrates of host pupillary reflex driven by photic stimulation of a retinal transplant; the second will correlate physiological responsiveness of the host brain to transplant stimulation and the anatomical correlates; the third will examine an adult sprouting situation; the fourth will study whether a retinal transplant can mediate a conditioned suppression response to light and the fifth study will use multiple transplants to create circuits. The work should provide fundamental understanding of the minimal substrates for visual function and further insight into the regenerative and plastic capacity of the visual system after damage either early in development or at maturity. It also explores transplantation strategies that might in time lead to ways of correcting visual deficits in humans.
