AFFERENT ORGANIZATION

这项提议旨在解决一个根本问题，即 目标特征，如细胞位置和数量，在 确定正态分布的发展和/或维护 以及该目标的传入的终末模式。攀缘纤维 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……里面 此外，还有一个很好的工具，就是突变的小鼠品系 基因决定的缺陷具有主要或次要的 导致正常小脑细胞结构发育失败 组织。这一组包括一些(织布工、交错织布工、卷筒工、 Lurcher)其中浦肯野细胞种群攀升的主要目标 光纤终端受到严重影响。通过分析组织结构 在这些突变和对照小鼠中的这个投射系统，我们希望 确定目标单元格位置和删除的影响(如果有的话) 目标传入系统的组织。要探索这一点 问题我们将在每个突变小鼠和对照小鼠中(1)分析 下橄榄复合体的定性和定量组织， (2)测定小脑浦肯野细胞的数量，从而 计算浦肯野细胞/下橄榄细胞比率和(3)与使用 的顺行技术分析了其分布和终末格局。 橄榄小脑投射的光镜和电子显微镜观察 技巧。这些研究应该为我们提供新的和重要的 有关目标单元格位置和目标单元格等变量是否 这些数字在确定一个单一的 传入来源及其目标。更广泛地说，这些研究表明 神经系统发育中的基本问题，如轴突 分布、靶点选择和突触形成。更好的 对关键的发展进程的理解 中枢神经系统的形成最终会导致更多 完全分析中枢神经系统的异常发育，并可能导致 这种不正常的发展可能被有益地操纵的方式。

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.