Mechanisms of Synaptic Processing in the Retina

视网膜突触处理机制

• 批准号: 8446969
• 负责人: William Rowland Taylor
• 金额: $ 36.58万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8446969
• 关键词: AMPA Receptors; Address; Affinity; Animal Model; Basic Science; Brain; Cells; Characteristics; Collaborations; Computer Simulation; Contrast Sensitivity; Data; Eye; Eye diseases; Frequencies; Glutamate Receptor; Glutamates; Goals; Heterogeneity; Human; Image; Investigation; Kainic Acid Receptors; Knowledge; Light; Measures; Mediating; Modeling; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neural Pathways; Neurobiology; Neurons; Oryctolagus cuniculus; Outcome; Output; Pathology; Pathway interactions; Pennsylvania; Photophobia; Physiological; Process; Property; Relative (related person); Research; Research Priority; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Role; Sampling; Signal Transduction; Stimulus; Synapses; Testing; Universities; Visual; Visual Fields; Work; base; cell type; ganglion cell; insight; kainate; novel; outer plexiform layer; receptive field; receptor; receptor function; response; selective expression; therapy development; transmission process; visual process; visual processing; voltage clamp

PROJECT SUMMARY This project addresses a basic research priority of the NEI, which is to understand how retinal networks process visual images. The mammalian retina contains about 20 different types of retinal ganglion cell each having characteristic receptive field properties. Most ganglion cell types are image- forming in that they comprise an array of essentially identical neurons that completely sample the visual field. Our approach has been to target specific, anatomically and physiologically identified ganglion cells, and perform quantitative analyses of the light-evoked inputs in order to gain insights into the connectivity and neural pathways that mediate physiological responses. In this proposal we will address three aims. Aim 1 proposes to test the hypothesis that selective expression of AMPA and kainate receptors in the outer plexiform layer contribute to temporal tuning in the ganglion cells. Aim 2 proposes to examine the role of NMDA receptors in generating the receptive field properties of direction-selective ganglion cells, and ON brisk-sustained ganglion cells. We will use subunit-specific antagonists to probe differences in NMDA receptor function in the ON and OFF pathways. Aim 3, in collaboration with Robert Smith at University of Pennsylvania, will use realistic computational models to predict the synaptic conductances, and estimate the magnitude of voltage-clamp errors in the ganglion cell recordings.

项目摘要 该项目涉及NEI的基础研究优先事项，即 了解视网膜网络如何处理视觉图像。哺乳动物的视网膜 包含约20种不同类型的视网膜神经节细胞， 典型的感受野特性大多数神经节细胞类型是图像- 形成的原因在于它们包括基本相同的神经元阵列， 对视野进行完整采样。我们的方法是针对具体目标， 解剖学和生理学上鉴定的神经节细胞，并执行 光诱发输入的定量分析，以便深入了解 连接和神经通路介导的生理反应。在这 建议我们将实现三个目标。目标1提出检验以下假设： 外丛状层AMPA和红藻氨酸受体的选择性表达 有助于神经节细胞的时间调谐。目标2建议审查 NMDA受体在产生感受野特性中的作用 方向选择性神经节细胞和ON brisk-sustained神经节细胞。我们将 使用亚单位特异性拮抗剂来探测NMDA受体功能的差异 在ON和OFF路径中。目标3，与罗伯特·史密斯合作， 宾夕法尼亚大学，将使用现实的计算模型来预测 突触电导，并估计电压钳误差的大小， 神经节细胞的记录