RETINOPETAL AXONS OF MAMMALIAN RETINAS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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顶叶轴突的功能。在最后一次授予期间，在大鼠和猴子的视网膜中发现了源自下丘脑神经元的含有组胺的轴突。为了确定这些输入的功能，在体外将外源性组胺应用于这些视网膜，同时从视网膜神经节细胞撤退。组胺最显著的作用之一是减少了猴子部分神经节细胞的光反应。拟议中的实验将确定这些细胞是否是阳伞细胞，它们对视觉的许多方面都有贡献，特别是对运动的感知。在光镜和电子显微镜下，组胺受体(HR)也定位于这些视网膜。在猴的视网膜血管和神经节细胞亚群中，HR1定位于内网状层的大斑点。表达这些受体的细胞将在拟议的解剖学实验中得到鉴定。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的许多类型的神经元。HR1也定位于杆状双极细胞的树突，组胺提高了这些细胞内的钙水平。拟议的生理学实验将研究其潜在机制，并寻找组胺对杆状双极细胞的其他影响。在这两个物种的视网膜中都有HR2的证据，这些证据将在拟议的解剖学实验中定位。在恒河猴双极细胞顶端的锥体蒂和杆状球体中发现了HR3，在第一突触处检测到光强度的增加。拟议的生理学实验将研究组胺对猕猴双极细胞的影响。综上所述，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视觉中的作用。研究猕猴视网膜血管上的组胺受体的实验特别重要，因为组胺已知会影响视网膜血流和毛细血管通透性。由于视网膜血管在许多眼病中功能异常，这一结果也可能具有临床意义。

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.