Circuit Assembly in the Vertebrate Retina

脊椎动物视网膜中的电路组装

• 批准号: 7455000
• 负责人: Rachel O Wong
• 金额: $ 29.22万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455000
• 关键词: Address; Aminobutyric Acid; Aminobutyric Acids; Animals; Arts; Axon; Behavior; Biological Assay; Brain Part; Cell physiology; Cells; Cellular Structures; Chromosome Pairing; Cues; DNA Sequence Rearrangement; Defect; Dendrites; Depth; Development; Diphtheria Toxin; Disease; Event; Feedback; Future; Genetic; Goals; Image; In Vitro; Interneurons; Investigation; Knowledge; Label; Lead; Life; Light; Location; Mediating; Methods; Microscopy; Modeling; Molecular; Mus; Mutant Strains Mice; Nervous System Part; Nervous system structure; Neuraxis; Neurites; Neurons; Neuropil; Output; Pathway interactions; Photoreceptors; Process; Proteins; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Rodent; Role; Sensory; Signal Transduction; Stratification; Structure; Synapses; Technology; Testing; Time; Tissues; Transgenic Mice; Transgenic Organisms; Trauma; Vision; Visual; Visual system structure; cell type; design; developmental disease; gamma-Aminobutyric Acid; horizontal cell; in vivo; insight; interdisciplinary approach; optical imaging; outer plexiform layer; promoter; receptor; recombinase; relating to nervous system; research study; retinal neuron; synaptic function; visual process; visual processing

DESCRIPTION (provided by applicant): The proper functioning of the central nervous system (CNS) requires that its many cellular components are connected appropriately, in order to process and encode information specific to each part of the brain. Thus, determining how the CNS is wired up precisely during development is fundamentally important. Although we have gained a significant understanding of the cellular and molecular mechanisms that are critical for circuit development, much has yet to be unraveled. Discovering these mechanisms requires approaches that will elucidate how cells interact with each other to form and maintain connections. Our long term goal is to understand how highly specific synaptic connections are established between the many cell types of the vertebrate retina, largely for 2 reasons: The retina is (1) essential for vision; and (2) its strongly correlated structure and function makes it an excellent model for investigating how neural cricuits are organized during development. In this proposal, we will focus on the first synaptic layer of the retina, the outer plexiform layer (OPL), within which visual signals are first processed in the visual system. In the OPL, photoreceptors contact bipolar cells that then relay signals along distinct pathways to retinal output cells. Horizontal cells modulate information conveyed from photoreceptors. Despite the importance of visual processing by the OPL, little is understood concerning its assembly during development. We propose to use and generate transgenic mice to examine how the various outer retinal cell types interact with each other to establish circuitry in the OPL. We will label photoreceptors, bipolar and horizontal cells in live animals, by causing them to express fluorescent proteins using cell-specific promoters. State-of-the-art optical imaging methods will be applied to visualize and follow how processes of these cells come to form appropriate contact with each other. We will also use and generate mutant mice to address the importance of horizontal cells, which develop earliest, in regulating the structural and functional development of the OPL. Our results should provide a deeper understanding of how interactions between cells lead to the establishment of their circuits, and thus provide further insight into developmental disorders in the nervous system. Our findings could potentially help focus future investigations aimed at designing strategies to re-establish retinal function in trauma or disease.

描述（由申请人提供）：中枢神经系统（CNS）的正常运作需要其许多细胞成分适当连接，以便处理和编码大脑每个部分特定的信息。因此，确定中枢神经系统在发育过程中是如何精确连接的是非常重要的。虽然我们已经对电路发展的关键细胞和分子机制有了很大的了解，但还有很多问题有待解决。发现这些机制需要阐明细胞如何相互作用以形成和维持连接的方法。我们的长期目标是了解如何在脊椎动物视网膜的许多细胞类型之间建立高度特异性的突触连接，主要有两个原因：视网膜是（1）视觉所必需的;（2）其强烈相关的结构和功能使其成为研究神经环在发育过程中如何组织的极好模型。在这个建议中，我们将集中在视网膜的第一个突触层，外丛状层（OPL），其中视觉信号首先在视觉系统中处理。在OPL中，光感受器接触双极细胞，双极细胞然后沿着沿着不同的通路将信号中继到视网膜输出细胞。水平细胞调节光感受器传递的信息。尽管OPL的视觉处理的重要性，很少有人了解它的组装过程中的发展。我们建议使用和产生转基因小鼠来研究各种外视网膜细胞类型如何相互作用，以建立OPL中的电路。我们将标记活体动物的光感受器、双极细胞和水平细胞，通过使用细胞特异性启动子使它们表达荧光蛋白。将应用最先进的光学成像方法来可视化和跟踪这些细胞的过程如何相互形成适当的接触。我们还将使用和产生突变小鼠，以解决水平细胞的重要性，最早发展，在调节OPL的结构和功能的发展。我们的研究结果应该提供更深入的了解细胞之间的相互作用如何导致其电路的建立，从而提供对神经系统发育障碍的进一步了解。我们的研究结果可能有助于未来的研究，旨在设计策略，以重建创伤或疾病中的视网膜功能。