CELL SURVIVAL IN A NEURAL CIRCUIT FOR LEARNING

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DESCRIPTION: The PI proposes to investigate the contribution of afferents and efferents to the survival of neurons during development of vocal behavior in male zebra finches. The time course of song development is well-understood and the nuclei involved have been identified. After the stereotypical song is learned cell numbers decrease in some nuclei. The sources of inputs and the targets of the nuclei have been previously identified. The PI proposes to remove particular inputs or target structures to determine the role that afferent fibers or target cells play in neuronal survival at different developmental time points. He will also initiate investigations to provide clues as to the mechanisms of cell death, which may be different in different nuclei. Four experiments are proposed. In the first, he will electrolytically lesion the telencephalic structure LMAN, which is the sole target of the thalamic nucleus DLM. The sole output of LMAN is the archistriatal nucleus, RA. He has shown that neurons in both DLM and RA die when LMAN is lesioned, if the lesion is made early in development. He provides preliminary evidence indicating that the mechanisms of cell death are different in the two structures. He will compare the amounts of protein synthesis, oxidative metabolism, and nucleic acid degradation in dying neurons of each structure to investigate whether cell death might occur through the synthesis of "killer proteins", or whether cells marked for death dramatically lower their overall metabolic and synthetic rates. In the second experiment, he will investigate why removal of LMAN in older birds does not result in cell death in RA as it does in young birds. His hypothesis is that late arriving afferents from HVC protect RA neurons in older animals from the effects of the removal of LMAN afferents. If so, lesions of both HVC and LMAN should cause RA neurons to die in older birds. If the dual lesions do not cause neuronal death, then an intrinsic change in RA neurons presumably occurred that makes them resistant to the detrimental effects of afferent removal. In the third experiment, he will attempt to determine whether the increased cell division that he has observed in RA following LMAN removal in young birds is due to increasing numbers of neurons or various glial types. He suspects that most of the dividing cells will eventually be glia, and to test this hypothesis he plans to combine thymidine labeling with specific glial markers. In the fourth experiment, he will determine whether the topographic specificity seen in the DLM to LMAN to RA pathway in adults is the result of an early abundance of connections that later get specifically pruned.