Development and Reorganization of Prenatal Visual System

产前视觉系统的发育和重组

基本信息

批准号：
6730498
负责人：
LEO M CHALUPA
金额：
$ 37.13万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-08-01 至 2006-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (adapted from applicant's abstract): The overall objective of the proposed research program is to further our understanding of the functional and structural development of retinal ganglion cells, the neurons that convey all information from the eyes to the visual centers of the brain. Five specific aims are proposed designed to fill major gaps in our current knowledge. As the first specific aim, patch-clamp recordings will be made from developing ganglion cells of the ferret in conjunction with their intracellular filling to allow for the morphological assessment of cells into major classes (alpha, beta and gamma) as well as On, Off and On-Off subtypes. Spontaneous activity patterns will be recorded at three well-defined stages of development and quantitative methods will be used to assess discharge patterns. The aim of this study is to determine whether different classes of cells manifest class-specific spontaneous activity patterns during the developmental period when activity mediated refinements are known to occur at retinorecipient structures. The second specific aim is to determine whether two intrinsic membrane properties studied during the past grant period (speed of recovery from Na-channel inactivation and Ca-mediated potassium currents) relate to the spontaneous activity patterns manifested by developing ganglion cells. The third specific aim is to determine how the visual responses of developing ganglion cells to flashing spots of light correlate with the stratification of dendrites in these neurons. In particular, we want to learn whether immature ganglion cells with dendrites ramifying within both the On and Off sublaminae of the developing IPL respond to the onset as well as the offset of flashing spots of light. The third specific aim is to determine whether the functional circuitry underlying On and Off responses in the developing retina is equivalent to that found in the mature retina. For this purpose, we will assess the effects of APB application on the light-evoked responses of morphologically identified ganglion cells. This glutamate agonist selectively blocks On responses in the mature retina, but preliminary results indicate that both On and Of f pathways can be effectively blocked by this drug in multistratified ganglion cells of the developing retina. The fifth specific aim is to determine whether cholinergic amacrine cells play a role in the formation of segregated On- and Off-cone bipolar cell axonal projections and in the stratification of retinal ganglion cell dendrites. To address this issue we have devised a novel method for eliminating cholinergic amacrine cells from the developing retina. The successful completion of this research program will provide new insights into the development of the mammalian retina, and it will also have implications for elucidating the cellular mechanisms underlying the formation of neuronal connections at higher levels of the nervous system.

描述（改编自申请人的摘要）：拟议的研究计划是为了进一步了解我们对功能和功能的理解视网膜神经节细胞的结构发展，传达所有的神经元从眼睛到大脑视觉中心的信息。五个具体 AIM旨在填补我们当前知识的主要空白。作为第一个特定目的是通过开发的贴片钳记录雪貂的神经节细胞与其细胞内填充到允许细胞形态学评估为主要类别（alpha，beta 和伽马）以及On-Off和On-Off子类型。自发活动模式将记录在三个明确的开发阶段，定量方法将用于评估放电模式。这个目的研究是确定不同类别的细胞是否表现在发育期间的特定班级自发活动模式当活动介导的细化发生在视网膜上时结构。第二个特定目的是确定是否有两个固有的在过去的赠款期间研究的膜特性（恢复速度从NA通道灭活和CA介导的钾电流中）与自发活性模式表现为神经节细胞。这第三个具体目的是确定如何发展的视觉响应神经节细胞闪烁的光点与分层相关这些神经元中的树突。特别是，我们想了解未成熟的带有树突的神经节细胞在sublaminae内和关闭开发的IPL响应发作以及闪烁的偏移光斑。第三个具体目的是确定功能是否发育中的视网膜中的开机和关闭响应的基础电路是相当于在成熟的视网膜中发现的。为此，我们将评估 APB应用对形态学上诱发的响应的影响鉴定出神经节细胞。这种谷氨酸激动剂有选择地阻止成熟视网膜中的反应，但初步结果表明这两者都在该药物可以有效地阻止F途径的多途径发育中的视网膜的神经节细胞。第五个具体目的是确定胆碱能无链氨酸细胞是否在隔离的形成中起作用在骨内和离子双极细胞轴突投影以及分层视网膜神经节细胞树突。为了解决这个问题，我们设计了一本小说消除发育中的视网膜中胆碱能无氨酸细胞的方法。该研究计划的成功完成将提供新的见解进入哺乳动物视网膜的发展，它也将阐明阐明细胞机制的影响神经元连接在神经系统的较高水平上的形成。