Structure and Function of Neurons in the Primate Retina

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的视觉信息处理。在这个资助期的重点将是在小神经节细胞，介导高灵敏度视觉和红绿色觉。侏儒神经节细胞是灵长类视网膜中最常见的细胞类型，但尽管经过多年的研究，关于提供它们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解决。第一个问题涉及从杆状细胞到小神经节细胞的输入来源。目前还不确定小神经节细胞是否通过突触从局部回路神经元（即无突细胞）接收杆状细胞的高度敏感输入，如果是，则在视网膜的什么地方首次出现。微型双极细胞和所有的无突细胞将使用猕猴视网膜的整个支架来标记，它们的接触将使用化学或电突触的第三种标记来标记。工作的假设是这些突触出现在没有杆的中央中央凹外面。另一种假设是，中央小神经节细胞仅通过相对不敏感的杆-锥间隙连接接收杆输入，但外周小神经节细胞通过AII细胞接收更敏感的杆输入。第二个问题涉及神经回路，它使小神经节细胞对红色和绿色视锥细胞的刺激产生相反的反应。在中央视网膜，兴奋是选择性的，因为小神经节细胞通过一个小双极细胞接收来自单个红色或绿色锥体的输入。但目前尚不清楚如何在外围产生选择性兴奋，在那里，小神经节细胞接受来自多个小双极细胞的输入。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，水平细胞和无突细胞，在它们的连接中是非选择性的。考虑到小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在上次拨款期间开发的神经回路线性模型。根据该模型，相对狭窄的树突区和分支遍布内丛状层的无突细胞使得小神经节细胞的反应比红绿锥体的分布预测的更加特异。虽然单个无突细胞使用抑制性神经递质甘氨酸，并且它们的连接是不选择性的，但它们的净效应是增强对一种锥体类型刺激的小神经节细胞的兴奋。目前的假设是，潜在的机制是抑制了第二种类型的无毛细胞的强直性、抑制性输入。这一假设将通过识别与小双极细胞和小神经节细胞突触前的甘氨酸能无突细胞，并研究它们与电路中其他无突细胞的相互作用来验证。由于人类和猕猴的视网膜非常相似，因此拟议的实验结果将与人类视觉有关。

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.