AFFERENT ORGANIZATION IN NEUROLOGICALS

神经系统突变体的传入组织分析 阐明了有趣的和潜在的揭示模型系统， 进一步的探索，无疑将使我们了解 重要机制的发展传入目标的关系。 在分析传入组织的发育过程中， lurcher橄榄小脑系统的传入-靶关系 突变小鼠，我们已经证明了一个特定的缺陷，在转座 橄榄小脑纤维从体突触接触到树突 突触 这种缺陷是传入特异性的，因为平行纤维 突触形成正常接触，膜特异性，作为正常突触 通过橄榄小脑纤维在浦肯野细胞索马上形成接触， 而不是其树突。 另一种突变体，蹒跚者，表现出某种程度的 与lurcher互补的缺陷，因为另一个主要的突触输入， 浦肯野细胞即平行纤维不发育。 因此在 有具体的，但不同的，改变的 浦肯野细胞的两个主要传入神经 另一种变种，蜿蜒尾巴，是 以小脑为特征， 部分不正常。 因此，它提供了一个不寻常的机会， 分析传入组织的正常和异常过程， 同一动物的传入-靶关系;内部对照，如果 你会的 该提案包含进一步分析传入系统的实验， 这些变种人 这些新的实验旨在：1）确定在 lurcher的突触发生中的特定缺陷的分子基础， 橄榄小脑纤维及其浦肯野细胞靶，2）确定是否 浦肯野氏病的时间脆弱性 lurcher中的细胞及其生化或位置的异质性， 3)确定突触发生缺陷的分子基础， 平行纤维和浦肯野细胞的交错，和4）检查 脊髓和橄榄小脑的组织和突触关系 meander tail突变小鼠中确定传入靶点的系统 目标控制下的特征。 考虑使用 神经突变体将使我们能够解决基本的问题， 传入系统的组织和发展。

The analysis of afferent organization in neurological mutants has illuminated interesting and potentially revealing model systems which, with further exploration, will undoubtedly provide us with an understanding of important mechanisms in the development of afferent-target relationships. In analyzing the developmental process of afferent organization and afferent-target relationships in the olivocerebellar system of the lurcher mutant mouse, we have demonstrated a specific defect in the transposition of the olivocerebellar fiber from somal synaptic contacts to dendritic synapses. This defect is both afferent specific, since parallel fiber synapses form normal contacts, and membrane specific, as normal synaptic contacts are formed by olivocerebellar fibers onto the Purkinje cell soma, but not its dendrite. Another mutant, the staggerer, exhibits a somewhat complementary defect to lurcher, in that the other major synaptic input to the Purkinje cell, namely the parallel fiber, does not develop. Thus in lurcher and staggerer there are specific, but different, alterations of the two major afferents to the Purkinje cell. Another mutant, meander tail, is characterized by a cerebellum which is partially normal cytoarcbitectually and partly abnormal. It therefore provides an unusual opportunity to analyze normal an abnormal processes of afferent organization and afferent-target relationship in the same animal; an internal control, if you will. This proposal contains experiments to further analyze afferent systems in these mutants. These new experiments are designed to: 1) determine in the lurcher the molecular basis of the specific defect in the synaptogenesis of olivocerebellar fibers and their Purkinje cell target, 2) determine if there is a relationship between the temporal vulnerability of Purkinje cells in the lurcher and their biochemical or positional heterogeneities, 3) determine the molecular basis of the synaptogeneic defect between parallel fibers and Purkinje cells in the staggerer, and 4) examine the organization and synaptic relationship of the spino and olivocerebellar systems in the meander tail mutant mouse to determine the afferent target characteristics which are under target control. The considered use of neurological mutants will enable us to address basic questions concerning the organization and development of afferent systems.