STRUCTURE AND FUNCTION OF PARALLEL CHANNELS IN THE FOVE

FOVE 中并行通道的结构和功能

• 批准号: 6518444
• 负责人: PETER STERLING
• 金额: $ 30.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6518444
• 关键词: Macaca; cell type; cyclic GMP; electron microscopy; electrophysiology; fovea centralis retinae; functional magnetic resonance imaging; guinea pigs; immunocytochemistry; membrane channels; neural information processing; neuroanatomy; retinal adaptation; retinal bipolar neuron; retinal ganglion; synapses; vision; visual pathways; visual stimulus; voltage gated channel

Our broad goal is to understand the circuits that link foveal cones to ganglion cells. Structural studies during the current period show the fovea to harbor multiple ganglion cell arrays. We suggest that each array signals a particular aspect of the visual scene and propose the following correspondences: high spatial frequency= midget (P) cell; low temporal frequency= parasol (M) cell; high temporal frequency= garland cell (M); hue= blue-yellow cell, red-green cell. We now plan to elucidate circuits for the remaining ganglion cells in our EM library and thus identify all the parallel channels from fovea to brain. We also plan to test these hypotheses by functional imaging of identified synapses: incubate retina with peroxidase tracer and briefly present a specific spatio-temporal-chromatic pattern to evoke exocytosis. As fused synaptic vesicles are retrieved by endocytosis, they sequester tracer which is fixed, and then visualized by confocal and electron microscopy. The ratio of labeled vesicles in different types of bipolar and amacrine synapse measures their relative release to a given stimulus. This approach, now being developed for a color-opponent circuit in guinea pig retina, will be applied to homologous circuits in primate retina. Finally, we plan to determine how the cGMP-gated channel contributes to a ganglion cell s visual response. Current through this channel is enhanced by nitric oxide and suppressed by glutamate through a novel mechanism (AMPA receptor coupled to a G-protein). We will identify the types of ganglion cell that express this current and determine which visual stimuli evoke and suppress it. The fovea occupies only two mm2 (0.3 percent) of the retina, but it supplies half of the visual cortex and is thus key to human vision. Knowing the functional architecture of its multiple, parallel circuits will help understand visual impairment (from conditions such as macular edema and age-related macular degeneration) and will ultimately contribute to the design of a retinal prosthesis.

我们的主要目标是了解连接中央凹视锥和神经节细胞的回路。 结构研究表明，在目前的时期，中央凹窝藏多个神经节细胞阵列。我们认为，每个阵列信号的视觉场景的一个特定方面，并提出以下对应关系：高空间频率=侏儒（P）细胞;低时间频率=阳伞（M）细胞;高时间频率=加兰细胞（M）;色调=蓝黄色细胞，红绿色细胞。 我们现在计划阐明我们的EM库中剩余的神经节细胞的电路，从而确定从中央凹到大脑的所有平行通道。我们还计划通过识别突触的功能成像来测试这些假设：用过氧化物酶示踪剂孵育视网膜，并简要地呈现特定的时空色模式以引起胞吐。 当融合的突触囊泡通过内吞作用被回收时，它们隔离固定的示踪剂，然后通过共聚焦和电子显微镜观察。 不同类型的双极和无长突突触中标记囊泡的比率测量它们对给定刺激的相对释放。这种方法目前正在为豚鼠视网膜的颜色对抗回路开发，将应用于灵长类动物视网膜的同源回路。 最后，我们计划确定cGMP门控通道如何有助于神经节细胞的视觉反应。通过该通道的电流被一氧化氮增强，并通过一种新的机制（AMPA受体与G蛋白偶联）被谷氨酸抑制。 我们将识别表达这种电流的神经节细胞的类型，并确定哪些视觉刺激引起和抑制它。中央凹只占视网膜的2平方毫米（0.3%），但它提供了一半的视觉皮层，因此是人类视觉的关键。 了解其多个并行电路的功能结构将有助于理解视力障碍（如黄斑水肿和年龄相关性黄斑变性），并最终有助于视网膜假体的设计。