MECHANISMS OF VISUAL SYSTEM MATURATION

这项研究的总体目标是了解 负责细胞模式发展的机制 以及神经系统中的连接。的发展。 外侧膝状核(LGN)的层和连接 为调查这些问题提供了一个合适的系统 机制，因为正常的系统是精确组织和 它的组织和发展的许多方面都很好- 有记录在案。我们在这个系统上的工作使我们假设 提出了层流形成机制的模型。每个人 旨在测试该模型的各个方面 树鼠和雪貂的发育期LGN。 特定的AIM 1将决定是否发育 传入神经和树突的生长顺序支持这一观点 这些过程以系统的方式相互作用，以产生 层间间隙。《特定目标2》将探讨其影响 视网膜传入对LGN细胞生长和间距的影响：a) 阻断轴浆运输；b)损害离散的视网膜 以及c)检查#年的区域和层流变化 胆碱能过程的个体发生。特定的AIM 3将 检查皮质和丘脑发育的影响 关于层间空间形成的投影：a)删除这些 输入；b)阻断动作电位；以及c)单眼 在发育早期对动物进行去核。最后，具体 目标4将探索建立体外培养的 LGN的模型(器官类型培养系统)检验 细胞结构和连接的发展 受控制的条件。 总之，这些研究将阐明层流的机制。 LGN的发展。这些结果反过来可能会提供 关于产生有序细胞的基本规则的线索 神经系统中的模式和连接。这些研究 不仅关系到理解 正常的视觉系统发育，也要理解 可能影响这一发育的临床疾病。

The overall objective of this research is to understand the mechanisms responsible for the development of cellular patterns and connections in the nervous system. The development of layers and connections in the lateral geniculate nucleus (LGN) provides an opportune system for investigation of these mechanisms, since the normal system is precisely organized and many aspects of its organization and development are well- documented. Our work on this system has led us to postulate a model that suggests the mechanisms of laminar formation. Each of the specific aims is designed to test aspects of this model in the developing LGN of tree shrews and ferrets. SPECIFIC AIM 1 will determine whether the developmental sequence of growth of afferents and dendrites supports the idea that these processes interact in a systematic way to produce interlaminar spaces. SPECIFIC AIM 2 will explore the influence of retinal afferents on LGN cell growth and spacing by: a) blocking axoplasmic transport; b) damaging discrete retinal regions; and c) examining for regional and laminar variations in the ontogenesis of cholinergic processes. SPECIFIC AIM 3 will examine the influence of developing cortical and collicular projections on interlaminar space formation by: a) deleting these inputs; b) blocking action potentials; and c) monocularly enucleating animals early in development. Finally, SPECIFIC AIM 4 will explore the feasibility of establishing an in vitro model (organotypic culture system) of the LGN to examine the development of cytoarchitecture and connections under controlled conditions. Together, these studies will clarify the mechanism of laminar development in the LGN. These results could, in turn, provide clues concerning the basic rules the produce orderly cellular patterns and connections in the nervous system. These studies are relevant not only to understanding basic mechanisms of normal visual system development, but also to understanding clinical disorders that may affect that development.