This is an anatomical and electrophysiological investigation of neuronal development, regeneration, repair, and competition. The system is the retina--optic nerve and tract--tectum of goldfish. This proposal takes advantage of two features of this system: the presence of spatial order (the tendency of axons from neighboring retinal ganglion cells to be run together in the nerve and to terminate together in the tectum) and the ability to regenerate (new axons when the original ones are cut, and new retina, following destruction of the original one). In the first part, experiments are proposed which should elucidate further the spatial order of the system. These involve fiber tracing by horseradish peroxidase (HRP) and electron microscopy, as well as single unit electrophysiological recordings. This extensive description of the normal provides a background for later investigations of regenerated tissue, which are guided by the question, """"""""How well is the order restored?"""""""" The most important fundamental issue which these experiments address is the role of axon pathway in the final selection of termination site, a question which is germane to all developing nervous systems. The second part deals with competition. When two eyes are forced surgically to innervate one tectal lobe, some of the terminals from each eye are excluded from patches of tectum. Exclusion through competition has been observed in many nervous sytems. In this proposal, the competition will be studied by visualizing the terminal arbors by HRP, for light and electron microscopic viewing. There are two health-related aspects. First, the basic phenomena of nervous system development, and especially competition, are germane any developmental disorder, such as amblyopia. Secondly, the failure of mammalian central nervous system to regenerate either axons or new nerve cells is fundamental to the irreversibility of many neuronal lesions in humans. By understanding better the process of regerneration in lower animals, we may one day be able to achieve the same for mammals, and use this therapuetically.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences B Study Section (VISB)
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University of Michigan Ann Arbor
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Ann Arbor
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Li, Z; Joseph, N M; Easter Jr, S S (2000) The morphogenesis of the zebrafish eye, including a fate map of the optic vesicle. Dev Dyn 218:175-88
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Hu, M; Easter, S S (1999) Retinal neurogenesis: the formation of the initial central patch of postmitotic cells. Dev Biol 207:309-21
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