DEVELOPMENT AND PATHOLOGY OF AXONS AND MYELIN

该提案要求支持一项持续的计划，该计划将审查 正常和病变神经轴突膜的发育 轴突膜分化与神经胶质细胞的关系 联合和髓鞘形成。 在过去的两年里，我们的研究 在以下领域取得进展：i）发育中CNS的生理学 有髓纤维; ii）发育中的中枢神经系统轴突膜超微结构 有髓纤维; iii）神经胶质细胞中的轴突和轴膜发育 缺乏环境; iv）髓鞘形成期间的轴-神经胶质关系; v） 再生轴突的生理学; vi）脱髓鞘纤维的生理学; vii）运动和感觉轴突的生理分化; viii） 非均匀纤维的导电性能。 的主要成果之一， 这些研究表明， 轴突膜在有髓纤维的发育过程中。 迄今为止 这种轴突膜分化和轴神经胶质细胞之间的关系 协会一直没有完全研究。 我们现在计划研究 轴突膜的分化，以及这种依赖性， 分化的神经胶质协会，在发展中的视神经和脊髓 线. 这些研究将利用若干补充技术 （冷冻断裂、细胞化学、电生理学、H3石房蛤毒素结合） 检查正常轴突和纤维中轴突膜的发育 它们是在神经胶质细胞缺乏的环境中发育的。 我们计划，在 这些研究，检查事件的顺序在分化的 有髓纤维的轴突膜，并确定是否（如果 因此，随着时间进程和特征）节点和结间 膜可以响应于延迟的神经胶质细胞鞘化而发育。 我们还计划研究H3 STX的发展与 结合和轴膜的冷冻断裂超微结构。 这些研究 将提供有关有髓鞘轴突正常发育的信息， 以及失去神经胶质接触的轴突的特征。 我们 我相信这些结果将有助于理解 膜的可塑性，这可能是重要的脱髓鞘疾病。

This proposal requests support for a continuing program which will examine the development of the axon membrane in normal and pathological nerve fibers, and the relationship of axon membrane differentiation to glial association and myelination. Over the past two years, our studies have led to progress in the following areas: i) physiology of developing CNS myelinated fibers; ii) axon membrane ultrastructure of developing central myelinated fibers; iii) axonal and axolemmal development in a glial deficient environment; iv) axo-glial relationships during myelination ; v) physiology of regenerating axons; vi) physiology of demyelinated fibers; vii) physiological differentiation of motor and sensory axons; viii) conduction properties of inhomogeneous fibers. One of the major results of these studies is the demonstration of a structural reorganization of the axon membrane during the development of myelinated fibers. To date, the relationship between this axon membrane differentiation and axo-glial association has remained incompletely studied. We now plan to examine the differentiation of the axon membrane, and the dependence of this differentiation on glial association, in developing optic nerve and spinal cord. These studies will utilize several complementary techniques (freeze-fracture, cytochemistry, electrophysiology, H3 saxitoxin binding) to examine axon membrane development both in normal axons, and in fibers which have developed in a glial cell deficient environment. We plan, in these studies, to examine the sequence of events in the differentiation of the axonal membrane of myelinated fibers, and to determine whether (and if so, with what time course and characteristics) nodal and internodal membrane can develop in response to delayed ensheathment with glial cells. We also plan to investigate the relationship between development of H3 STX binding, and freeze-fracture ultrastructure of the axolemma. These studies will provide information about the normal development of myelinated axons, and the characteristics of axons which are deprived of glial contact. We believe that these results will be relevant to understanding mechanisms of membrane plasticity which may be important in the demyelinating diseases.