Synaptic Inputs to Retinal Ganglion Cells

视网膜神经节细胞的突触输入

• 批准号: 7683196
• 负责人: RICHARD Harry MASLAND
• 金额: $ 36.4万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683196
• 关键词: Acetylcholine; Adult; Affect; Amacrine Cells; Brain; Cells; Clinical; Code; Conflict (Psychology); Dendrites; Disease model; Event; Excitatory Synapse; GABA Antagonists; GABA-A Receptor; Genes; Goals; Half-Life; Individual; Inhibitory Synapse; Label; Laboratory Study; Laws; Learning; Location; Maintenance; Methods; Modeling; Normal tissue morphology; Oryctolagus cuniculus; Physiological; Positioning Attribute; Proteins; RNA Interference; Research; Retina; Retinal; Retinal Ganglion Cells; Sampling; Site; Source; Stimulus; Synapses; Synaptic Vesicles; System; Testing; Transgenic Animals; Varicosity; Vesicular Transport Proteins; Visual; cell type; cholinergic; gamma-Aminobutyric Acid; ganglion cell; gene gun; knock-down; mature animal; neurotransmitter release; postsynaptic; presynaptic; research study; response

DESCRIPTION (provided by applicant): The ganglion cells of mammalian retinas exist in roughly a dozen types, each transmitting a different encoding of the visual scene to the brain. The long-term goal of this research is to learn the mechanism by which specific types of ganglion cells achieve these codlings. We have developed an interface incubation system that allows maintenance of multiple samples of adult rabbit retinas for several days in an unsupervised, culture-like system. Genes coding for RNAi or tagged synapse proteins are biolistically transfected into individual retinal ganglion cells. Two questions involve the synaptic events underlying directional selectivity in certain retinal ganglion cells. First, we propose to use RNAi to knock down GABAergic or cholinergic responsiveness in individual ganglion cells. Recording will reveal the contribution of these direct (postsynaptic) inputs to direction selectivity. Second, we will investigate the co-release of GABA and Ach by the starburst amacrine cells. Are the two neurotransmitters released from the same cellular sites or different ones? This will be studied by localizing their vesicular transport proteins. The third question is a more general one. Our recent experiments suggest that the excitatory inputs to ganglion cell dendrites are spatially distributed according to an even-spacing law: the synapses seem to repel each other. In addition, they systematically avoid branch points in the dendritic arbor. We now propose to see if these rules apply to all types of ganglion cells; to model their physiological consequences; and to see if the same rules apply to inhibitory synapses. The methods introduced here can be used in adult animals of any species. They obviate the need for transgenic animals, increase the number of samples that can be simultaneously studied, and allow labeling of proteins that have long half-lives. They can be used in normal tissue or in disease models. We hope that they will be useful to laboratories studying both basic and clinical problems.

描述（由申请人提供）：哺乳动物视网膜的神经节细胞大约存在十几种类型，每种类型都将视觉场景的不同编码传输到大脑。这项研究的长期目标是学习特定类型的神经节细胞实现这些代码的机制。我们已经开发了一个接口孵化系统，该系统允许在一个无监督的，类似培养的系统中维持多个成年兔视网膜样品几天。编码RNAi或标记的突触蛋白的基因被生物存在转染到单个视网膜神经节细胞中。 两个问题涉及某些视网膜神经节细胞中定向选择性的突触事件。首先，我们建议使用RNAi在单个神经节细胞中击倒GABA能或胆碱能反应。记录将揭示这些直接（突触后）输入对方向选择性的贡献。其次，我们将通过Starburst Amacrine细胞研究GABA和ACH的共释放。两个神经递质是从相同的细胞位点释放的吗？这将通过定位其囊泡转运蛋白来研究。 第三个问题是一个更一般的问题。我们最近的实验表明，对神经节细胞树突的兴奋性输入是根据均匀间距的定律空间分布的：突触似乎相互驱逐。此外，它们系统地避免了树突状乔木中的分支点。现在，我们建议查看这些规则是否适用于所有类型的神经节细胞。建模其生理后果；并查看相同的规则是否适用于抑制突触。 此处介绍的方法可用于任何物种的成年动物。它们消除了对转基因动物的需求，增加了可以同时研究的样品数量，并允许标记具有半衰期的蛋白质。它们可用于正常组织或疾病模型。我们希望它们对研究基本问题和临床问题的实验室有用。