Prenatal Development of Visual System

视觉系统的产前发育

• 批准号: 6969510
• 负责人: LEO M CHALUPA
• 金额: $ 37.88万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969510
• 关键词: Macaca mulatta; brain mapping; developmental neurobiology; immunotoxicity; in situ hybridization; mammalian embryology; microarray technology; neurogenesis; retina; synaptogenesis; visual pathways

DESCRIPTION (provided by applicant): The objective of the proposed research program is to further our understanding of the cellular and molecular mechanisms underlying the formation of specific retinogeniculate projections in the primate visual system. We will focus on the development of the two major functional streams, magnocellular (M) and parvocellular (P), which at maturity are a hallmark of the primate visual system. In Specific Aim 1, we will utilize modern neuroanatomical tracing methods in combination with pre- and postsynaptic molecular markers to learn how the formation of M and P pathways relates to synapse formation in the dLGN. Our working hypotheses are: (i) that eye-specific inputs form in the P pathway earlier than in the M pathway, and (ii) that selective ingrowth of retinal fibers into the P and/or M subdivisions of the dLGN occurs prior to synaptogenesis. In Specific Aim 2 we will define the spatiotemporal properties of retinal activity during the time that retinal axons selectively innervate the M and P segments of the dLGN. If correlated retinal activity is observed at this early stage of development, we will assess the effects of perturbing and also blocking such activity on the formation of M and P retinogeniculate projections using a novel immunotoxin developed in our laboratory. The foregoing experiments will tell us whether or not neuronal activity plays a role in the development of these two functionally distinct pathways. In Specific Aim 3 we will utilize DNA microarrays and in situ hybridization methods to find molecular cues expressed in the developing dLGN during the period when M and P pathways are being formed. The proposed research program will break new ground by increasing our understanding of the mechanisms underlying the formation of M and P pathways which are a distinguishing feature of the primate visual system.

描述（由申请人提供）：拟议研究计划的目的是进一步了解灵长类动物视觉系统中特定视网膜投射形成的细胞和分子机制。我们将重点关注大细胞（M）和细细胞（P）这两个主要功能流的发展，这两个功能流的成熟是灵长类视觉系统的标志。在具体目标 1 中，我们将利用现代神经解剖学追踪方法结合突触前和突触后分子标记来了解 M 和 P 通路的形成如何与 dLGN 中的突触形成相关。我们的工作假设是：（i）眼睛特异性输入在 P 通路中形成早于 M 通路，以及（ii）视网膜纤维选择性向内生长到 dLGN 的 P 和/或 M 细分中发生在突触发生之前。在具体目标 2 中，我们将定义视网膜轴突选择性支配 dLGN 的 M 和 P 段期间视网膜活动的时空特性。如果在发育的早期阶段观察到相关的视网膜活动，我们将使用我们实验室开发的新型免疫毒素来评估扰动和阻断此类活动对 M 和 P 视网膜形成投射的影响。上述实验将告诉我们神经元活动是否在这两种功能不同的途径的发展中发挥作用。在具体目标 3 中，我们将利用 DNA 微阵列和原位杂交方法来寻找 M 和 P 途径形成期间发育中 dLGN 中表达的分子线索。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来开辟新的领域，M 和 P 通路是灵长类视觉系统的一个显着特征。