Amacrine cell signaling

无长突细胞信号传导

• 批准号: 6914997
• 负责人: EVANNA L GLEASON
• 金额: $ 22.05万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6914997
• 关键词: amacrine cells; calcium flux; calcium indicator; calcium ion; cell cell interaction; cell component structure /function; chick embryo; confocal scanning microscopy; electrophysiology; gamma aminobutyrate; immunocytochemistry; membrane channels; mitochondria; neural information processing; neural transmission; synapses; tissue /cell culture; voltage /patch clamp

DESCRIPTION (provided by applicant): Retinal amacrine cells are interneurons that help to shape the visual signal that ganglion cells send to other visual centers in the brain. The ultimate goal of the research proposed here is to understand the factors that underlie the dynamics of calcium and calcium dependent signaling within and between amacrine cells. A better understanding of signal processing in the retina will be valuable in helping us to better understand how signals are shaped elsewhere in the brain. This proposal specifically addresses the role of mitochondria in shaping the temporal and spatial properties of calcium signals and calcium-dependent processes in amacrine cells. Mitochondria are especially interesting because they can be a spatially discrete sink and source of calcium. This is relevant to amacrine cell function in particular because it is thought that much of the synaptic signaling in amacrine cells is spatially localized rather than spread over broad regions of the cell. To understand the role of mitochondria in amacrine cell signaling, we propose the following three specific aims: Specific Aim 1: To elucidate the impact of mitochondrial calcium buffering on the spatial and temporal aspects of calcium elevations in amacrine cells. Specific Aim 2: To discover the role of mitochondrial calcium buffering during synaptic transmission between GABAergic amacrine cells. Specific Aim 3: To uncover the interactions between mitochondria and other mechanisms and organelles relevant to calcium signaling in amacrine cells. To achieve these three aims, amacrine cells cultured from the chick retina will be used as a model system for amacrine cells in the intact retina. This system will allow the examination of single amacrine cells or pairs of amacrine cells participating in functional GABAergic synapses, an extremely common type of synapse found in the retina. The proposed research will employ calcium imaging, whole cell voltage clamp recordings, immunocytochemistry and confocal microscopy to achieve the stated aims. These studies will lead to insights into the mechanisms that underlie the processing of the visual signal in the vertebrate retina.

描述（由申请人提供）：视网膜无大细胞是中间神经元，有助于塑造神经节细胞发送到大脑其他视觉中心的视觉信号。这里提出的研究的最终目的是了解钙和钙依赖性信号的动力学基础的因素。对视网膜中信号处理的更好理解对于帮助我们更好地理解信号如何形成大脑中的信号将是有价值的。该建议专门解决了线粒体在塑造钙信号和钙依赖性过程的时间和空间特性中的作用。线粒体特别有趣，因为它们可以是空间离散的下沉和钙的来源。这特别是与无链氨酸细胞功能有关，因为它认为无长熟细胞中的许多突触信号在空间上是局部定位的，而不是分布在细胞的宽区域上。为了了解线粒体在无大细胞信号传导中的作用，我们提出了以下三个特定目的：特定目的1：阐明线粒体钙缓冲对无链氨基细胞钙升高的空间和时间方面的影响。特定目的2：发现线粒体钙缓冲在GABA能小核细胞之间的突触传播过程中的作用。特定目标3： 发现线粒体与其他机制与细胞器之间的相互作用与无链氨酸细胞中的钙信号相关。为了实现这三个目标，从鸡视网膜中培养的无长熟细胞将用作完整视网膜中的无长熟细胞的模型系统。该系统将允许检查参与功能性GABA能突触的单个无分支细胞或成对的无长熟细胞，这是一种在视网膜中发现的突触的极为常见类型。拟议的研究将采用钙成像，全细胞电压夹记录，免疫细胞化学和共聚焦显微镜来实现既定目标。这些研究将导致对脊椎动物视网膜视觉信号处理的机制的见解。