CELL SURVIVAL IN A NEURAL CIRCUIT FOR LEARNING

描述：PI建议研究以下因素的贡献 在发育过程中神经元存活的传入和传出 雄性斑胸草雀的发声行为。歌曲发展的时间进程 已经被很好地理解，并且所涉及的细胞核已经被识别。后 典型的歌曲是习得性的，有些细胞核中的细胞数量减少。 输入的来源和核的目标以前已经被 鉴定PI建议删除特定输入或目标 结构，以确定传入纤维或靶细胞的作用， 在不同发育时间点的神经元存活中发挥作用。他 还将启动调查，以提供有关机制的线索 在不同的细胞核中可能是不同的。 提出了四个实验。首先，他将电解 病变端脑结构LMAN，这是唯一的目标， 丘脑核LMAN的唯一输出是archistriatal 核、RA。他已经表明，当LMAN时，DLM和RA中的神经元都会死亡， 如果病变是在发育早期造成的，他提供 初步证据表明，细胞死亡的机制是 两种结构不同。他会比较 死亡中的合成、氧化代谢和核酸降解 每个结构的神经元，以研究细胞死亡是否可能发生 通过“杀手蛋白”的合成，或者细胞是否标记为 死亡大大降低了他们的整体代谢和合成率。 在第二个实验中，他将研究为什么去除LMAN， 年老的鸟类不会像年轻的鸟类那样导致RA细胞死亡 鸟 他的假设是，来自HVC的延迟传入保护了 老年动物中的RA神经元受到去除LMAN的影响 传入神经 如果是这样的话，HVC和LMAN的病变应该会导致RA神经元 死在老鸟身上如果双重损伤不引起神经元死亡， 那么RA神经元可能发生了内在的变化， 它们抵抗传入神经移除的有害影响。在 第三个实验，他将试图确定是否增加 细胞分裂，他观察到在RA后，LMAN去除年轻 鸟类是由于增加数量的神经元或各种神经胶质类型。 他怀疑大多数分裂的细胞最终将是神经胶质， 为了验证这一假设，他计划将联合收割机胸苷标记与 特异性神经胶质标志物 在第四个实验中，他将确定 是否在DLM到LMAN到RA中观察到的地形特异性 成年人的神经通路是早期大量连接的结果 之后会被特别修剪

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.