AFFERENT ORGANIZATION IN NEUROLOGICALLY MUTANTS

一些非常有趣的实验结果和观察 关于橄榄小脑投射的组织， 突变小鼠（见进展报告）导致了实验， 这种延续。 我们相信这些新实验是合乎逻辑的 和令人兴奋的延伸的传入组织的研究， 神经学小鼠突变体。 他们专门针对 关于靶细胞的正确生成（卷轴），神经纤维- 靶细胞识别（lurcher）和突触发生（staggerer）， 所有这些都是正常组织的重要特征 传入系统 (1)在reeler中，迁移是 被认为是主要缺陷，我们发现，在 成年人的浦肯野细胞数量减少了50% 而橄榄小脑的组织和地形 投影一般都是保留的。 本提案将审查 导致（细胞死亡）和/或细胞生成减少） 浦肯野细胞数。 在这样做的时候，我们要解决的问题是， 无论是正常的数量生成还是靶细胞的存活 人口是必要的适当迁移和安置， 群体（2）在lurcher中，所有浦肯野细胞死亡的突变体 出生后第二至第十二周，橄榄小脑 投影似乎终止于 分子层和颗粒层。 地形和副地形 带状组织似乎基本上得到了保留。 新 该提案中的实验旨在确定是否 在发育过程中（a）这些传入神经曾经进入分子 层并与浦肯野细胞树突相关联，以及（B）如果它们 不要，买免疫学和生化分析来确定 这些树枝状突起中存在什么分子缺陷 通过橄榄小脑纤维识别和“攀爬”。 (3)在 staggerer，一种以小脑死亡为特征的突变体 颗粒细胞，浦肯野氏细胞未能形成三级棘 细胞和大多数浦肯野细胞的死亡，仍然存在 存在着一个不完整的，parasounds和地形适当的（在 一般）橄榄小脑投射的组织。 在这 我们计划继续探索突触发生中的缺陷 平行纤维-浦肯野细胞之间， 免疫学和生物化学方法，分子差异 在正常小鼠和蹒跚小鼠中。 考虑使用 神经突变体将使我们能够解决基本的问题 关于传入系统的组织和发展。

Some very intriguing results and observations from experiments concerning the organization of the olivocerebellar projection in mutant mice (see Progress Report) have led to the experiments in this continuation. These new experiments, we believe, are logical and exciting extensions of the study of afferent organization in neurological mouse mutants. They specifically address questions concerning proper generation of target cells (reeler), nerve fiber- target cell recognition (lurcher) and synaptogenesis (staggerer), all of which are important characteristics of a normally organized afferent system. (1) In reeler, a mutant in which migration is considered to be the primary defect, we have discovered that, in the adult there is a 50% reduction in the number of Purkinje cells while the organization and topography of the olivocerebellar projection is generally preserved. This proposal will examine the cause (cell death) and/or decreased cell generation) of decreased Purkinje cell number. In doing so we address the question of whether proper numerical generation or survival of a target cell population is necessary for proper migration and placement of that population (2) In lurcher, a mutant in which all Purkinje cells die postnatally during the second to twelfth weeks, the olivocerebellar projection appears to terminate in plexuses at the border of the molecular and granular layers. The topographic and parasagittal zonal organization appears to be generally preserved. The new experiments in this proposal are designed to determine whether during development (a) these afferents ever enter the molecular layer and associate with Purkinje cell dentrites and (b) if they do not, to determine buy immunological and biochemical analyses what molecular deficiency exists in these dentrites to preclude recognition and "climbing" by olivocerebellar fibers. (3) In staggerer, a mutant characterized by the death of cerebellar granule cells, the failure to develop tertiary spines on Purkinje cells and the death of the majority of Purkinje cells, there still exists a patchy, parasagittal and topographically appropriate (in general) organization of the olivocerebellar projection. In this continuation we plan to explore the defect in synaptogenesis between the parallel fiber-Purkinje cells by examining via immunological and biochemical approaches, the molecular differences in the staggerer and normal mice. The considered use of neurological mutants will enable us to address basic questions concerning the organization and development of an afferent system.