MECHANISMS OF VISUAL SYSTEM MATURATION

主要目标是定义视觉模式通过哪些机制 连接是在开发期间建立的。这个程序是一个 我们继续努力解释外侧膝状体(LGN)是如何形成的 层层形成。我们将使用6层树鼠LGN作为模型系统 因为所有细胞6层都是在出生后发育的。三个具体目标的审查 视网膜传入如何影响细胞层的形成。在目标1，研究 是为了阐明连接的序列和细节 发育中的LGN细胞。应用HRP和~3H氨基酸进行产前研究 示踪剂将检查最初的视网膜传入分离。产后 利用HRP的研究将检查单个终末的形态 核内的视网膜、顶盖和皮质轴突的树枝。另外， 将使用示踪剂来检查纹状体LGN神经支配的序列 大脑皮层。目标2将提供关于细胞数量调节的信息 以及在LGN层形成过程中视网膜和LGN的细胞死亡。最后， 目标3将测试视网膜传入可能滋养的不同方式 通过1)操纵视神经活动(暗培养)影响LGN靶点 或河豚毒素注射)，2)阻断轴浆运输 (秋水仙碱)，3)破坏离散的视网膜区域。在所有情况下，LGN小区 将检查蛋鸡的发育和细胞分化以 确定这些操作的有效性。 总而言之，这些研究应该会提供一个更清晰的图景，说明层压是如何 在LGN内发展；结果反过来可能提供以下线索 感觉传入影响细胞学的基本规律 突触后靶点高度有序的分化和定位 系统。因此，这些研究不仅与理解 视觉正常发育的基本机制，临床上也要 了解可能影响发育的障碍。

The major objective is to define mechanisms by which patterns of visual connections are established during development. This program is a continuation of our efforts to explain how lateral geniculate nucleus (LGN) layers form. We will use the 6 layered tree shrew LGN as a model system since all cell 6 layers develop postnatally. The 3 specific aims examine how retinal afferents influence cell layer formation. In Aim 1, studies are proposed to elucidate the sequence and details of connections of developing LGN cells. Prenatal studies utilizing HRP and 3H amino acid tracers will examine initial retinal afferent segregation. Postnatal studies utilizing HRP will examine the morphology of individual terminal arbors of retinal, tectal, and cortical axons within the nucleus. Also, tracers will be used to examine the sequence of LGN innervation of striate cortex. Aim 2 will provide information on the regulation of cell number and cell death in the retina and LGN during LGN layer formation. Finally, Aim 3 will test different ways in which retinal afferents might trophically influence LGN targets by 1) manipulating optic nerve activity (darkrearing or tetrodotoxin injection), 2) blocking of axoplasmic transport (colchicine), 3) damaging discrete retinal regions. In all cases, LGN cell layer development and cytologic differentiation will be examined to determine the effectiveness of these manipulations. Together these studies should provide a clearer picture of how lamination develops within the LGN; results which in turn could provide clues as to basic rules by which sensory afferents influence the cytologic differentiation and topography of postsynaptic targets in a highly ordered system. As such, these studies are relevant not only to understanding basic mechanisms of normal visual development, but also clinically to understanding disorders that may effect that development.