AFFERENT ORGANIZATION

这项建议旨在解决一个根本问题，即 目标特性，例如细胞位置和数量， 确定正态分布的发展和/或维持 和终端模式的一个传入到该目标。 攀爬纤维 从下橄榄复合体到小脑的投射是理想的， 这种类型的分析，因为它是一个高度具体的投影系统。 在 此外，还有一个很好的工具，即突变品系的小鼠， 基因决定的缺陷主要或次要 导致正常小脑细胞结构发育失败， organization. 包括在这一组是一些（织布机，交错，卷轴， lurcher），其中浦肯野细胞群，攀登的主要目标 光纤终端受到严重影响。 通过分析组织结构， 我们希望这些突变小鼠和对照小鼠的这种投射系统 确定靶细胞位置和缺失在细胞凋亡中起什么作用， 对目标的传入系统的组织。 探索这个 问题，我们将在每个突变和对照小鼠（1）分析 下橄榄复合体的定性和定量组织， (2)确定小脑中浦肯野细胞的数量， 计算浦肯野细胞/下橄榄细胞比率，以及（3）使用 顺行技术分析的分布和终端模式， 橄榄小脑投射光镜和电镜观察 技术. 这些研究应该为我们提供新的和重要的 关于诸如目标小区位置和 这些数字在确定一个单一的 传入源和它的目标。 更普遍的是，这些研究表明， 神经系统发育中的基本问题，如轴突 分布、目标选择和突触形成。 更好的 了解关键的发展过程，有助于 中枢神经系统的形成最终会导致一个更 全面分析中枢神经系统的异常发育， 可以有利地操纵这种异常发展的方式。

This proposal is designed to address the fundamental question of whether target characteristics such as cell position and number are critical in determining the development and/or maintenance of the normal distribution and terminal pattern of an afferent to that target. The climbing fiber projection from the inferior olivary complex to the cerebellum is ideal for this type of analysis since it is a highly specific projection system. In addition, there exists an excellent tool, namely, mutant strains of mice in which a genetically determined defect has either primarily or secondarily caused a failure in the development of normal cerebellar cytoarchitectonic organization. Included in this group are some (weaver, staggerer, reeler, lurcher) in which the Purkinje cell population, the main target of climbing fiber terminations is severely affected. By analyzing the organization of this projection system in these mutant and control mice we expect to determine what effects, if any, target cell position and deletion play in the organization of an afferent system to that target. To explore this question we will, in each of the mutant and control mice (1) analyze the qualitative and quantitative organization of the inferior olivary complex, (2) determine the number of Purkinje cells in cerebellum and thereby calculate the Purkinje cell/inferior olive cell ratio and (3) with the use of anterograde techniques analyze the distribution and terminal pattern of the olivocerebellar projection using light and electron microscopic techniques. These studies should provide us with new and important information concerning whether variables such as target cell position and number which are critical in determining the relationship between a single afferent source and its target. More generally, these studies speak to basic issues in the development of the nervous system such as axonal distribution, target selection and synapse formation. A better understanding of the critical developmental processes which contribute to the formation of the central nervous system will eventually lead to a more complete analysis of abnormal development of the CNS and perhaps lead to ways in which such abnormal development may be beneficially manipulated.