RETINOPETAL AXONS OF MAMMALIAN RETINAS

哺乳动物视网膜的视网膜轴突

• 批准号: 7716080
• 负责人: DAVID W MARSHAK
• 金额: $ 0.71万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716080
• 关键词: Affect; Amacrine Cells; Axon; Blood flow; Brain; Calcium; Capillary Permeability; Cells; Chromosome Pairing; Computer Retrieval of Information on Scientific Projects Database; Dendrites; Dopamine; Electron Microscopy; Employee Strikes; Eye diseases; Funding; Goals; Grant; Histamine; Histamine Receptor; Hypothalamic structure; In Vitro; Inner Plexiform Layer; Institution; Light; Localized; Macaca; Mammals; Monkeys; Motion Perception; Neurons; Pathway interactions; Physiological; Primates; Rattus; Research; Research Personnel; Resources; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Role; Source; Synapses; Testing; United States National Institutes of Health; Vision; clinically significant; ganglion cell; insight; light intensity; receptor; research study; response; retina blood vessel structure; retinal neuron; retinal rods

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long term goal of these experiments is to understand the functions of axons projecting from the brain to the retina, or retinopetal axons. During the last grant period, axons originating from neurons in the hypothalamus and containing histamine were identified in rat and monkey retinas. To determine the functions of these inputs, exogenous histamine was applied to these retinas in vitro while receding from retinal ganglion cells. One of the most striking effects of histamine was the reduction of the light responses in a subset of ganglion cells in monkeys. The proposed experiments will determine whether these are the parasol cells, which contribute to many aspects of vision, particularly the perception of motion. Histamine receptors (HR) were also localized in these retinas by light and electron microscopy. HR1 were localized to large puncta in the inner plexiform layer, a subset of ganglion cells and retinal blood vessels in monkeys. The cells expressing those receptors will be identified in the proposed anatomical experiments. In rat retinas, HR1 receptors were localized to dopaminergic amacrine cells, and the proposed experiments will test the hypothesis that they are inhibitory. This would greatly amplify the effects of histamine because dopamine influences so many types of neurons in the retina. HR1 were also localized to dendrites of rod bipolar cells, and histamine raised intracellular calcium levels in these cells. The proposed physiological experiments will investigate the underlying mechanism and look for other effects of histamine on rod bipolar cells. There is evidence for HR2 in retinas of both species, and these will be localized in the proposed anatomical experiments. HR3 were found at the apex of ON bipolar cell dendrites in cone pedicles and rod spherules of monkeys, at the first synapse in the pathway detecting increments in light intensity. The proposed physiological experiments will study the effects of histamine on macaque bipolar cells. Taken together, these experiments will provide the first comprehensive description of the mechanism by which axons from the brain act on retinal neurons in mammals and provide insight into their roles in primate vision. The experiments dealing with histamine receptors on macaque retinal blood vessels are particularly important because histamine is known to affect retinal blood flow and capillary permeability. Because retinal blood vessels function abnormally in many eye diseases, the results may also be clinically significant.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 这些实验的长期目标是了解从大脑投射到视网膜的轴突或视网膜轴突的功能。在最后的资助期间，在大鼠和猴子的视网膜中发现了源自下丘脑神经元并含有组胺的轴突。为了确定这些输入的功能，在体外将外源性组胺施加到这些视网膜上，同时从视网膜神经节细胞中撤出。组胺最显着的作用之一是减少猴子神经节细胞的光反应。拟议的实验将确定这些是否是伞细胞，伞细胞有助于视觉的许多方面，特别是运动感知。通过光学和电子显微镜观察，组胺受体（HR）也位于这些视网膜中。 HR1 定位于内丛状层的大点，这是猴子神经节细胞和视网膜血管的一个子集。表达这些受体的细胞将在拟议的解剖实验中被鉴定。在大鼠视网膜中，HR1 受体定位于多巴胺能无长突细胞，拟议的实验将检验它们具有抑制性的假设。这将极大地放大组胺的作用，因为多巴胺影响视网膜中多种类型的神经元。 HR1 也定位于杆状双极细胞的树突，组胺提高了这些细胞的细胞内钙水平。拟议的生理实验将研究潜在的机制并寻找组胺对杆双极细胞的其他影响。有证据表明这两个物种的视网膜中都存在 HR2，并且这些将在拟议的解剖实验中进行定位。 HR3 被发现于猴子锥蒂和杆状小球中 ON 双极细胞树突的顶端，位于检测光强度增量的通路中的第一个突触处。拟议的生理实验将研究组胺对猕猴双极细胞的影响。总而言之，这些实验将首次全面描述大脑轴突作用于哺乳动物视网膜神经元的机制，并深入了解它们在灵长类动物视觉中的作用。处理猕猴视网膜血管上的组胺受体的实验特别重要，因为已知组胺会影响视网膜血流和毛细血管通透性。由于许多眼部疾病中视网膜血管功能异常，因此结果也可能具有临床意义。