1985 — 1986 |
Easter, Stephen S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Visual System: Order, Regeneration, and Competition @ University of Michigan At Ann Arbor
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.
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0.958 |
1986 — 1987 |
Easter, Stephen S |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Research Training-Biological Sciences @ University of Michigan At Ann Arbor |
0.958 |
1987 — 1991 |
Easter, Stephen S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of the Visual and Ocular Motor System @ University of Michigan At Ann Arbor
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.
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0.958 |
1993 — 1996 |
Easter, Stephen S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of the Visual System @ University of Michigan At Ann Arbor
This work is intended to increase our understanding of the development of the optic chiasm and tract. The projection from the retina to the brain is essential for sight, and the highly ordered nature of the axons' trajectories and terminations are key to the formation of connections that make spatial vision possible. The retinofugal projection is thought to resemble all central nervous system projections, so a study of its development relates to central nervous system development generally. Developmental disorders can not be understood without knowledge of the normal developmental processes, and this proposal is intended to reveal them. It is an anatomical study in which light and electron microscopy and immunocytochemistry are used to study three key players. First, the formation of the projection is initiated by a small set of "pioneer" axons originating from 5-10 ganglion cells in the retina; experiments in this proposal should elucidate their role in leading the vastly more numerous axons that follow them. Second, the retinal axons pass alongside a pre-existing tract in the brain on their way to the optic tectum; the work proposed here will reveal more about that pre-existing tract and about its role in guiding the growing axons. Third, a structurally distinct zone alongside the pre-existing tract has recently been discovered, and this is where the retinal axons grow; the work here will investigate the importance of that zone in guiding the axons and assess the generality of such a structure for other cases of axonal guidance. Most of the work is carried out in the embryonic zebrafish (Brachydanio rerio), chosen because of its technical advantages and because early development is thought to be very similar in all vertebrates. Where possible, the conclusions will be checked in other vertebrates: frog, chick, and mouse.
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0.958 |
1995 — 1999 |
Easter, Stephen S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Initial Tract Formation in the Vertebrate Brain @ University of Michigan At Ann Arbor
DESCRIPTION (Investigator's Abstract): The focus of this proposal is on the earliest axon pathways that are formed in the brain, as small groups of well- defined neurons project axons to form specific and very reproducible tracts. Of particular interest is a longitudinal boundary which separates axons into separate longitudinal tracts. 1. The general mechanisms that guide the axons will be defined by a series of experimental surgeries in chick embryos, designed to distinguish between three possible classes of cues. 2. The trajectories of the early axons in chick and mouse will be compared to the expression patterns of adhesion molecules which have a potential role in axon guidance. 3. The function of the longitudinal boundary in axon guidance will be tested by altering its location by surgery (in chick embryos) or analysis of a genetic mutant (in mice). 4. The interactions of the axons with the boundary will be examined, both by describing the morphology of the leading growth cones, and by describing the cellular environment at the boundary. 5. A number of potential genetic regulatory genes have been previously reported, and here their expression pattern will be correlated with the axon patterns at the boundary. This work will be done on both the embryonic chicken, chosen because of its convenience, low price, and the potential for experimental surgery, and the embryonic mouse, chosen because of the wealth of genetic mutants, both natural and human-engineered, with defects shared by human diseases.
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0.958 |