The primary goal of the proposed experiments is to understand the influences that regulate axonal growth under conditions of normal development, as well as in a system that has been experimentally stressed. The hamster visual system is the system of choice because of data already available on its ontogenesis. Moreover, we have detailed information on plastic changes obtainable after early lesions of central visual-system structures. In particular, we will (I) examine the role of axo- axonal interactions in determining the mature projection pattern of single axons; (II) investigate the extent to which subpopulations of ganglion cells exhibit differences in ability to alter their growth after neonatal lesions; (III) evaluate the role of specific proteins in the elongation, arborization and abnormal regrowth of these axons. Retinofugal axons begin to arborize in the midbrain tectum several days prior to the arrival of neocortical afferents. A detailed morphogenetic study of both populations will serve as a basis for evaluating developmental changes in each one subsequent to surgical removal of the other. Interactions between the two populations will also be analysed after neonatal tectal ablations or brachial cuts, both of which delay and alter ingrowth of the afferents. Altered growth will be characterized within the framework of the elongation and arborization modes of development. We will look for differences in the ability of large versus small retinal cells in exhibiting plastic alterations. Lastly, the role of GAP/B-50, a protein present at elevated levels during axon growth, will be evaluated with the aid of immunohistochemical localization of the protein during times when axons are undergoing morphological changes in a normal or an experimentally manipulated environment. These experiments will reveal further rules controlling mammalian nervous system development and elucidate how these rules apply to altered growth following externally inflicted damage.
