RETINOPETAL AXONS OF MAMMALIAN RETINAS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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到视网膜的轴突或视网膜顶轴突的功能。在最后一个给予期，在大鼠和猴子视网膜中发现了起源于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，外源性组胺被应用于这些视网膜体外，同时从视网膜神经节细胞退去。组胺最显著的作用之一是减少猴子神经节细胞子集的光反应。拟议的实验将确定这些是否是遮阳伞细胞，遮阳伞细胞对视觉的许多方面都有贡献，特别是对运动的感知。在光镜和电镜下，组胺受体（HR）也定位于这些视网膜。HR1定位于猴子内丛状层的大点、神经节细胞亚群和视网膜血管。表达这些受体的细胞将在拟议的解剖实验中进行鉴定。在大鼠视网膜中，HR1受体定位于多巴胺能无突细胞，本实验将验证它们具有抑制性的假设。这将极大地增强组胺的作用，因为多巴胺会影响视网膜中许多类型的神经元。HR1也定位于杆状双极细胞的树突，组胺提高了这些细胞的细胞内钙水平。提出的生理实验将研究潜在的机制，并寻找组胺对杆状双极细胞的其他影响。有证据表明，HR2在这两个物种的视网膜，这些将定位在拟议的解剖实验。HR3在猴锥体蒂和杆状球体的ON双极细胞树突顶端，在光强增加通路的第一个突触上被发现。拟建的生理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动物视觉中的作用。研究猕猴视网膜血管上的组胺受体的实验尤为重要，因为我们知道组胺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，因此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.