A major theme in developmental neurobiology is the dependence of neurons on target-derived factors for survival during embryonic life. Two unanswered questions about this trophic relationship are whether neuronal dendritic arbors are regulated by these same signals and whether the dependence of neurons on these factors is lifelong. Over the next five years, I intend to address these related questions using two classes of neurons, sympathetic ganglion cells and somatic motor neurons. Sympathetic ganglion cells have been chosen because a trophic molecule for these neurons, nerve growth factor (NGF) has been purified and is readily available. Motor neurons will be studied because their easily accessible efferent projections make analysis of their dependence on target-derived factors straightforward. Trophic influences on the dendritic arborization of sympathetic ganglion cells will be assessed directly by administering NGF and NGF antiserum to developing animals. The effects of target- derived factors on the dendritic arborization of somatic motor neurons will be studied by analyzing arbors after experimentally induced increases and decreases in the number of skeletal muscle fibers innervated by these neurons. Dendritic arbors will be revealed by intracellular iontophoresis of horseradish peroxidase or Lucifer Yellow and by retrograde transport of ligand- conjugated tracers. Studies on trophic dependencies in maturity will be carried out by long term injections of NGF antiserum in the case of sympathetic ganglia and by permanent target deprivation of somatic motor neurons. Neuronal survival will be assessed in conventional histologic preparations of ganglia, brainstem, and cranial nerve roots after variable periods of trophic deprivation. All of these studies will require utilization of the CORE Resource. Analysis of dendritic arbors will be carried out by computer-assisted 3 dimensional reconstructions, determination of total dendritic lengths and quantitation of other branching parameters. The studies on survival will also utilize computer- assisted morphometry to assess neuronal atrophy.
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