A long-term goal of this project is to explain the anatomical and behavioral effects of brain damage suffered in fetal or perinatal life. This requires an understanding of how nerve fibers (axons) develop, and how they respond to brain damage. Thus, the project's focus is on the growth of axons in both normal and abnormal situations, and on the consequences of abnormal axonal development. The claim that the optic tract can regenerate in a mammal if it is transected very early in life, but not once a critical age is reached, will be investigated. If true regeneration is found, it will be compared with normal development, for major fiber groups in the visual system. No regrowth is found after a critical age, but it has been discovered that axon regeneration can be induced by surgical implants containing a growth factor (FGF). Just how late in development this regeneration can be obtained, and whether it can be influenced to produce a restoration of lost connections, will be examined using implants of embryonic tissue or cultured cell lines, or of agents of block recently discovered growth inhibitors. The role of a cell type found in large numbers only in the developing brain, the radial cell (radial glia), in axon growth and in regeneration, will be explored. The possibility that different neuronal cell types in the retina give rise to axons with different potentials for regeneration or for abnormal termination (by collateral sprouting) will be examined, with the possibility in mind that a selective growth after brain damage could have important behavioral consequences. The finding that early brain lesions damaging the optic tract, and subsequent regrowth of this tract to the midbrain, cause hamsters to show supersensitivity to potential predators, will be further investigated. In pursuing these aims, new techniques that could yield very novel information about axonal growth and regeneration will be explored: methods of imaging growth axons in the living brain, brain implants of cells grown in culture with special properties, and a new way to block activity of growing axons in an attempt to increase their regrowth.
