A major goal of this project is to explain the development of mammalian visual system axons and their connections in terms of basic principles that can be used to understand how this sequence of development is altered by early brain damage. In addition, we aim to specify how the altered development affects behavior, and to use the early-damaged brain as a means for elucidating the nature of subcortical vision. New, related studies of plastic changes induced in the adult visual system are particularly promising for future application to the major health problem of functional restoration after brain injury. Using the hamster optic tract as a model, experiments are designed to relate damage-induced neuronal plasticity during development to two distinct modes of axon growth. Regeneration of long tracts appears to be possible only for axons in the earlier mode of rapid, fasciculated elongation; experiments are designed to find out whether this mode can be extended or reinstated by early axon transection, or by inducing transected axons in the adult retina to regenerate within a peripheral nerve implant. Sensitive behavioral methods will be used to assess recovery of vision which may be subserved by induced regeneration in adult animals. Even after the age at which regeneration (without implants) fails, sprouting into denervated tissue can still occur, seemingly by axons which are in the second mode of growth, characterized by reduced rate and by progressive arborization and terminal formation. Mean for altering this growth mode will also be explored. Intrinsic differences in axons in different growth states will be examined in a study of proteins rapidly transported by the axons to the terminals; specific proteins may differ in the two modes of growth. Detailed descriptions of morphological transformations are being undertaken with the aid of techniques for filling single axons with tracer substances (HRP, PHA-L). In other experiments, new techniques will be employed to distinguish subpopulations of retinal ganglion cells and their axons which may follow different rules during development or during regeneration or sprouting. The model systems created by neonatal lesions will also be exploited to extend basic knowledge of subcortical vision, its sparing or alteration after neonatal lesions, and its recovery following neocortical lesions in adults.
