AFFERENT ORGANIZATION IN NEUROLOGICALLY MUTANTS

一些非常耐人寻味的实验结果和观察结果 关于橄榄球小脑投射的组织 突变的小鼠(见进展报告)导致了在 这个续集。我们相信，这些新的实验是符合逻辑的。 传入组织研究的令人振奋的扩展 神经性小鼠突变体。他们专门解决问题 关于靶细胞(卷轴)的正确生成，神经纤维- 靶细胞识别(步行者)和突触发生(交错者)， 所有这些都是一个正常组织的 传入系统。(1)在卷轴上，一个突变体，其中迁徙是 被认为是主要缺陷，我们发现，在 成人的浦肯野细胞的数量减少了50% 而橄榄小脑的组织和地貌 投影通常被保留下来。这项提案将审查 减少的原因(细胞死亡)和/或细胞生成减少 浦肯野细胞编号。在这样做的过程中，我们解决了 无论是目标细胞的适当数量生成或存活 人口对于适当的迁移和安置是必要的 Lurcher中的种群(2)，其中所有浦肯野细胞都死亡的突变体 在出生后的第二到第十二周，橄榄小脑 投影似乎终止于 分子层和颗粒层。地形图和副矢状图 地带性组织似乎大体上得到了保留。新的 该方案中的实验旨在确定 在发育过程中(A)这些传入细胞曾经进入分子 并与浦肯野细胞树状突起相关联，以及(B)如果它们 不要，要确定买来的免疫学和生化分析 这些树状石中存在什么分子缺陷来阻止 橄榄小脑纤维的识别和“攀登”。(3)在 一种以小脑死亡为特征的突变体 颗粒细胞--浦肯野三级棘突发育不全 细胞和大多数浦肯野细胞的死亡，仍然存在 存在一个斑驳的、旁矢状面和适当的地形(在 一般)橄榄球小脑投射的组织。在这 继续，我们计划探索突触发生的缺陷 平行纤维-浦肯野细胞之间的通孔检查 免疫学和生化方法，分子差异 在摇摇晃晃和正常的小鼠身上。经过深思熟虑的使用 神经学突变将使我们能够解决基本问题 关于组织和发展传入系统的问题。

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.