GROWTH OF OPTIC NERVE FIBERS

视神经纤维的生长

基本信息

批准号：
2160651
负责人：
ROBERT W. WILLIAMS
金额：
$ 18.77万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 1995-11-30
项目状态：
已结题

项目摘要

We propose to continue studies of a remarkable mutation of the mammalian visual system in which the entire retinal projection is uncrossed. This drastic inborn error is associated with a marked and persistent nystagmus. A systematic analysis of the visual system of these achiasmatic animals is important for at least two reasons. First, the mutation provides us with a unique natural experiment that is ideal for testing important ideas about the major processes that guide retinal axons at the optic chiasm early in development. We will determine how, when, and why axons fail to cross the midline in mutants. Both light and electron microscopy and several tract tracing methods will be used to perform a systematic structural analysis of the embryonic retina, optic stalk, and chiasm. The analysis should provide insight into the genesis of the norma mammalian chiasm, as well as into the genesis of the severe, decussation error seen in human albinos. This developmental analysis should also provide us with a critical test of the hypothesis that pigmentation controls pathways chosen by retinal axons early in development. The second important reason to study this mutation is that it provides us with a unique system in which to test many current ideas about the formation of topographic representations in the CNS. In particular, the mutation provides a superb model with which to validate, reject, or modify hypotheses about the role of axon-target interactions, nasal-temporal rivalry, and binocular competition in partitioning visual nuclei and the visual cortex into sets of visuotopic representations. We will use physiological recording methods and complementary tract tracing methods to determine the functional and structural repercussions that result from the drastic decussation error. In specific, we will determine how nasal and temporal retinal axons from the same retina organize themselves in two retinorecipient nuclei-the dorsal lateral geniculate nucleus and the superior colliculus. This will be followed by high resolution mapping studies of visuotopic representations in the primary visual cortex of mutants. This systematic analysis of retinotopy in mutants will provide us with a way to assess the plasticity of visual maps and will also provide us a way to critically test several important hypotheses regarding the formation of topographic representations. In summary, the achiasmatic mutant provides us with a powerful means to test influential ideas regarding the development, function, and plasticity of the vertebrate visual system. In addition, this mutation shows great promise as an animal model for congenital nystagmus in humans. The mutants may ultimately help us in developing and testing new methods to treat oculomotor disturbances in humans.

我们建议继续研究哺乳动物的显着突变整个视网膜投影未划过的视觉系统。这严重的先天误差与标记和持续的眼球震颤有关。对这些恰当动物的视觉系统的系统分析是至少有两个原因很重要。首先，突变为我们提供了独特的自然实验是测试有关重要想法的理想选择早期指导视网膜轴突的主要过程发展。我们将确定轴突如何，何时以及为什么无法越过突变体中线。光和电子显微镜以及几道示踪方法将用于执行系统的结构分析胚胎视网膜，视觉茎和Chiasm。分析应提供深入了解Norma哺乳动物chiasm的起源，以及在人白化病中看到的严重的，de骨误差的起源。这发展分析还应为我们提供对色素沉着控制视网膜轴突选择的途径的假设发展初期。研究这种突变的第二个重要原因是它为我们提供了具有独特的系统，可以测试许多有关有关的当前想法中枢神经系统中地形表示形成。特别是突变提供了一个出色的模型，可以通过该模型来验证，拒绝或修改关于轴突 - 靶标相互作用的作用，鼻 - 时空的作用的假设竞争和双眼竞争，以分区视觉核和视觉皮层成一组视觉表示。我们将使用生理记录方法和互补道追踪方法确定由急剧的pe骨误差。具体而言，我们将确定鼻和来自同一视网膜的颞视网膜轴突在两个视网膜分离核 - 背侧侧向核和上丘。随后将进行高分辨率映射对主要视觉皮层的视觉表示的研究突变体。突变体中视网膜的系统分析将为我们提供通过评估视觉图的可塑性的方法，还将为我们提供一种批判性检验几个重要假设的方法形成地形表示。总而言之，恰当突变体为我们提供了一种强大的手段测试有关发展，功能和可塑性的有影响力的想法脊椎动物视觉系统。此外，该突变显示出很棒的作为人类先天性眼球震颤的动物模型的承诺。突变体最终可能会帮助我们开发和测试新方法来治疗人类的动眼障碍。