Structure and Function of Neurons in the Primate Retina

灵长类动物视网膜神经元的结构和功能

• 批准号: 7986655
• 负责人: DAVID W MARSHAK
• 金额: $ 31.15万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7986655
• 关键词: Accounting; Address; Amacrine Cells; Antibodies; Automobile Driving; Axon; Cells; Chemical Synapse; Chemicals; Color Visions; Dendrites; Diagnosis; Electrical Synapse; Electrodes; Electron Microscopy; Electrons; Electroretinography; Excitatory Synapse; Eye diseases; Gap Junctions; Glutamate Receptor; Glycine; Goals; Grant; Human; Immunolabeling Technics; In Vitro; Individual; Inhibitory Synapse; Inner Plexiform Layer; Label; Life; Light; Linear Models; Macaca; Mediating; Methods; Microscopic; Modeling; Monitor; Morphology; Neurons; Neurotransmitters; Parvalbumins; Pathway interactions; Pattern; Perikaryon; Peripheral; Physiological; Preparation; Presynaptic Terminals; Primates; Process; Research; Retina; Retinal Cone; Source; Stratification; Structure; Synapses; Techniques; Testing; United States; Varicosity; Vertebrate Photoreceptors; Vision; Work; abstracting; base; calretinin; connexin 36; density; fovea centralis; ganglion cell; gephyrin; horizontal cell; lucifer yellow; neural circuit; neurobiotin; presynaptic; receptive field; recoverin protein; research study; response; retinal rods; treatment effect; visual information

DESCRIPTION (provided by applicant): The goal of these experiments is to understand the processing of visual information in primate retinas. The focus in this grant period will be on midget ganglion cells, which mediate both high acuity vision and red-green color vision. Midget ganglion cells are the most common type in primate retinas, but despite many years of research, a number of important questions about the neural circuit providing their input remain unanswered. Two of these questions will be addressed in the proposed anatomical experiments. The first question deals with the source of the input from rods to midget ganglion cells. It is uncertain whether midget ganglion cells receive highly-sensitive input from rods via synapses from local circuit neurons, AII amacrine cells, onto midget bipolar cells and if so, where in the retina this first appears. Midget bipolar cells and AII amacrine cells will be labeled using whole mount preparations of macaque retina, and their contacts will be labeled using a third marker for either chemical or electrical synapses. The working hypothesis is that these synapses appear just outside the rod-free, central fovea. An alternative hypothesis is that central midget ganglion cells receive rod input only via relatively insensitive rod-cone gap junctions, but peripheral midget ganglion cells receive more sensitive rod input via AII cells. The second question deals with neural circuit that generates opposing responses of midget ganglion cells to stimulation of red and green cones. In the central retina, the excitation is selective because midget ganglion cells receive input from a single red or green cone via a single midget bipolar cell. But it is uncertain how selective excitation would be generated in the periphery, where midget ganglion cells receive input from more than one midget bipolar cell. It is unclear how selective inhibition arises anywhere in the retina because the inhibitory local circuit neurons, horizontal cells and amacrine cells, are unselective in their connections. The working hypothesis to account for the selectivity of midget ganglion cell responses is based on results from physiological experiments in other mammalian retinas and a linear model of the neural circuit developed during the last grant period. According to the model, amacrine cells with relatively narrow dendritic fields and branches throughout the inner plexiform layer make the responses of midget ganglion cells more specific than would be predicted by the distribution of the red and green cones. Although individual amacrine cells use the inhibitory neurotransmitter glycine and are unselective in their connections, their net effect is to enhance excitation of the midget ganglion cell in response to stimulation of one cone type. The working hypothesis is that the underlying mechanism is inhibition of a tonic, inhibitory input by a second type of amacrine cell. This hypothesis will be tested by identifying the glycinergic amacrine cells presynaptic to midget bipolar cells and midget ganglion cells and studying their interactions with other amacrine cells in the circuit. Because the retinas of humans and macaques are so similar, the results of the proposed experiments would be relevant to human vision. PUBLIC HEALTH RELEVANCE: This research deals with the neural circuit that generates the light responses of midget ganglion cells. These are, by far, the most common type of ganglion cells in humans and other primates, and they mediate both high acuity vision and red-green color vision. The experiments on the origin of rod inputs to midget ganglion cells would help to understand vision in dim light, when both rods and cones are active. In the United States, this is particularly important for driving at night, and problems with vision in dim light are an early sign for many eye diseases. These experiments would also help to explain the mechanism underlying the electroretinogram, a widely-used method to diagnose eye diseases and monitor the effects of treatments.

描述（由申请人提供）：这些实验的目的是了解灵长类动物视网膜视觉信息的处理。本次资助期间的重点将是介导高敏锐度视觉和红绿色视觉的侏儒神经节细胞。小型神经节细胞是灵长类动物视网膜中最常见的类型，但尽管经过多年的研究，有关提供其输入的神经回路的许多重要问题仍未得到解答。其中两个问题将在拟议的解剖实验中得到解决。第一个问题涉及从杆到小型神经节细胞的输入来源。目前尚不清楚小型神经节细胞是否通过来自局部回路神经元、AII无长突细胞的突触接收来自杆的高度敏感输入到小型双极细胞，如果是的话，它首先出现在视网膜的哪个位置。小型双极细胞和所有无长突细胞将使用猕猴视网膜的整体制备物进行标记，并且它们的触点将使用用于化学或电突触的第三个标记进行标记。有效的假设是这些突触出现在无杆的中央凹之外。另一种假设是，中央侏儒神经节细胞仅通过相对不敏感的视杆-视锥间隙连接接收视杆输入，但外周侏儒神经节细胞通过 AII 细胞接收更敏感的视杆输入。第二个问题涉及神经回路，该神经回路产生小型神经节细胞对红色和绿色视锥细胞刺激的相反反应。在中央视网膜中，兴奋是选择性的，因为小型神经节细胞通过单个小型双极细胞接收来自单个红色或绿色视锥细胞的输入。但尚不确定如何在外周产生选择性兴奋，其中小型神经节细胞接收来自多个小型双极细胞的输入。目前还不清楚选择性抑制是如何在视网膜的任何地方产生的，因为抑制性局部回路神经元、水平细胞和无长突细胞的连接是非选择性的。解释侏儒神经节细胞反应选择性的工作假设是基于其他哺乳动物视网膜的生理实验结果和上一个资助期间开发的神经回路的线性模型。根据该模型，无长突细胞具有相对狭窄的树突区域和遍布内丛状层的分支，使得小型神经节细胞的反应比红色和绿色视锥细胞的分布所预测的反应更加具体。尽管单个无长突细胞使用抑制性神经递质甘氨酸并且其连接是非选择性的，但它们的净效应是增强小型神经节细胞对一种视锥细胞类型的刺激的兴奋。工作假设是，潜在的机制是第二种类型的无长突细胞抑制强直性、抑制性输入。该假设将通过识别突触前的小型双极细胞和小型神经节细胞的甘氨酸无长突细胞并研究它们与回路中其他无长突细胞的相互作用来检验。由于人类和猕猴的视网膜非常相似，因此所提出的实验结果将与人类视觉相关。 公共健康相关性：这项研究涉及产生侏儒神经节细胞光反应的神经回路。迄今为止，它们是人类和其他灵长类动物中最常见的神经节细胞类型，它们介导高敏锐度视觉和红绿色视觉。关于小型神经节细胞视杆细胞输入起源的实验将有助于理解弱光下的视觉，此时视杆细胞和视锥细胞都处于活动状态。在美国，这对于夜间驾驶尤为重要，昏暗光线下的视力问题是许多眼部疾病的早期征兆。这些实验还将有助于解释视网膜电图的潜在机制，视网膜电图是一种广泛使用的诊断眼部疾病和监测治疗效果的方法。