Prenatal Development of Visual System

描述(申请人提供)：所有离开眼睛的视觉信息都通过视网膜神经节细胞(RGC)的活动来传递。在人类和其他视觉系统高度发达的动物中，视网膜节细胞属于功能上不同的类别，它们选择性地对视觉环境中的不同特征做出反应。这项拟议的研究计划的目标是确定猕猴视网膜神经节细胞的产前成熟以及促进M细胞和P细胞分化的机制。我们将重点介绍灵长类RGC的两大类，M类和P类。这项拟议的研究涉及三组实验。第一个主要的系列实验(特定目标1)将检验这样的假设，即视网膜节细胞在出生前对视觉刺激有反应，具有类似M和P反应特性的细胞在出生前就开始分化。第二系列实验(特定目标2)将测试M和P RGC在其固有的膜特性上表现出类别特异性差异的假设，并且这些差异在出生之前就出现了。最后，第三系列实验将验证M和P RGC表达与不同视觉功能的发育、内在生理特性和与这些不同视觉通路相关的形态差异相关的类别特异性基因的假设。拟议的研究计划将通过增加我们对M和P通路形成机制的理解而开辟新的天地，M和P通路是灵长类视觉系统的一个显著特征。鉴于视网膜神经节细胞对视觉的核心重要性，我们必须了解在发育过程中引导它们分化的机制，因为发育过程中的障碍是影响视力和视觉处理的几种疾病的基础。

DESCRIPTION (provided by applicant): All visual information leaving the eye is conveyed in the activity of retinal ganglion cells (RGCs). In humans and other animals with a highly developed visual system, RGCs belong to functionally distinct classes that respond selectively to different features in the visual environment. The objective of the proposed research program is to determine the prenatal maturation of RGCs in the macaque monkey and the mechanisms that contribute to M and P cell differentiation. We will focus on the two major classes of primate RGCs, the M and P classes. The proposed study involves three sets of experiments. The first major series of experiments (Specific Aim 1) will test the hypothesis that RGCs are responsive to visual stimuli before birth and the differentiation of cells with M-like and P-like response properties begins before birth. The second series of experiments (Specific Aim 2) will test the hypothesis that M and P RGCs express class-specific differences in their intrinsic membrane properties and these differences emerge before birth. Finally, the third series of experiments will test the hypothesis that M and P RGCs express class-specific genes related to the development of distinct visual function, intrinsic physiological properties and morphological differences associated with these distinct visual pathways. The proposed research program will break new ground by increasing our understanding of the mechanisms underlying the formation of the M and P pathways which are a distinguishing feature of the primate visual system. Given the central importance of retinal ganglion cells for vision, it is important that we understand the mechanisms that guide their differentiation during development, as disorders during development underlie several illnesses affecting vision and visual processing.