Mechanisms of Neurotransmission in Vertebrate Retina

脊椎动物视网膜神经传递机制

• 批准号: 7230923
• 负责人: RUTH HEIDELBERGER
• 金额: $ 32.44万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230923
• 关键词: ATP Hydrolysis; Address; Area; Back; Biological Models; Calcium; Cells; Chromosome Pairing; Communication; Complex; Dependence; Dyes; Electric Capacitance; Elements; Endocytosis; Endosomes; Exocytosis; Funding; Glutamates; Goals; Human; Hydrostatic Pressure; Indium; Kinetics; Knowledge; Location; Measurement; Membrane; Methods; Molecular; Monitor; Mus; Mutation; Neurons; Organelles; Pathway interactions; Phosphatidylinositols; Phosphotransferases; Photoreceptors; Physiological; Positioning Attribute; Preparation; Process; Protein Isoforms; Proteins; Research; Research Project Grants; Retina; Retinal; Retinal Diseases; Retinal Photoreceptors; Retrieval; Role; SNAP receptor; Signal Transduction; Surface; Synapses; Synaptic Vesicles; Testing; Time; Vertebrate Photoreceptors; Vesicle; Vision; Vision Disorders; Visual; design; flash photolysis; neurotransmission; neurotransmitter release; presynaptic; programs; retinal rods; ribbon synapse; synaptotagmin; transmission process; visual information

DESCRIPTION (provided by applicant): Calcium-regulated release of neurotransmitter is a fundamental feature of synaptic communication. How this process is regulated presynaptically is not yet fully understood, particularly at the ribbon-style synapses of retinal photoreceptors and bipolar cells. These synapses differ from conventional synapses in several important ways, including the expression of unusual isoforms of key synaptic proteins and the absence of other synaptic proteins. Thus, it is not clear to what extent knowledge of presynaptic mechanisms obtained in other model systems can be extrapolated to these neurons. Furthermore, mutations in some of these unusual proteins are associated with human retinal disease. The long-term goal of this research project is to understand how visual information is transferred across the retina. In this proposal, we examine mechanisms of exocytosis and synaptic vesicle dynamics in bipolar cells and photoreceptors of the vertebrate retina. This information will reveal aspects of presynaptic design that allows these neurons to release glutamate rapidly and for extended periods of time. A combination of biophysical, ultrastructural, and molecular approaches are used. Specific goals are to examine the mechanisms underlying the requirement for ATP hydrolysis in maintaining neurotransmitter release and endocytosis in ON-bipolar cells. Because endocytosis may contribute to the supply of active zone synaptic vesicles in addition to preserving membrane surface area, mechanisms of membrane retrieval in bipolar cells and photoreceptors will also be examined. To allow us to determine in what ways photoreceptors are adapted for tonic release and to define those presynaptic mechanisms that are hallmarks of retinal ribbon synapses, synaptic vesicle dynamics in photoreceptors will be examined and compared with those of bipolar cells and conventional synapses. Finally, we will develop the mouse bipolar cell as a preparation for biophysical study of presynaptic mechanisms. This will position us to study presynaptic mechanisms at the molecular level and examine the role of specific synaptic proteins implicated in disorders of vision.

描述（由申请人提供）：神经递质的钙调节释放是突触通信的基本特征。该过程的调节方式尚未完全理解，特别是在视网膜感受器和双极细胞的带状突触下。这些突触不同于常规突触以几种重要的方式不同，包括关键突触蛋白的异常同工型和其他突触蛋白的表达。因此，尚不清楚在其他模型系统中获得的突触前机制的知识在多大程度上可以推断到这些神经元中。此外，其中一些不寻常蛋白的突变与人类视网膜疾病有关。该研究项目的长期目标是了解如何在视网膜上传输视觉信息。在此提案中，我们检查了脊椎动物视网膜的双极细胞和感光体中胞吐作用和突触囊泡动力学的机制。这些信息将揭示突触前设计的各个方面，这些方面使这些神经元可以快速释放谷氨酸释放并长时间释放。使用了生物物理，超微结构和分子方法的组合。具体的目标是检查ATP水解在维持双极细胞中神经递质释放和内吞作用方面的需求的基础机制。由于内吞作用还可能有助于有效区域突触囊泡的供应，除了保留膜表面积外，还将检查双极细胞中膜检索的机理和感光体。为了使我们能够确定光感受器的适应性释放，并定义那些是视网膜色带突触标志的突触前机制，将检查并与双极细胞和传统突触的突触囊泡动力学相比。最后，我们将开发小鼠双极细胞，以准备突触前机理的生物物理研究。这将使我们在分子水平上研究突触前机制，并检查与视力障碍有关的特定突触蛋白的作用。