STRUCTURE AND FUNCTION OF PARALLEL CHANNELS IN THE FOVE

我们的主要目标是了解连接中央凹锥体和神经节细胞的电路。在这一时期的结构研究显示，中央凹内有多个神经节细胞阵列。我们建议，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=小(P)细胞；低时间频率=阳伞(M)细胞；高时间频率=花环细胞(M)；色相=蓝黄细胞，红绿细胞。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，并简要呈现特定的时空-颜色模式来唤起胞外分泌。当融合的突触囊泡通过内吞作用被回收时，它们会隔离固定的示踪剂，然后通过共聚焦显微镜和电子显微镜观察。标记囊泡在不同类型的双相和无峰突触中的比例测量了它们对给定刺激的相对释放。这种方法，目前正在开发豚鼠视网膜上的颜色对抗电路，将应用于灵长类动物视网膜上的同源电路。最后，我们计划确定cgmp门控通道如何促进神经节细胞的视觉反应。通过该通道的电流通过一氧化氮增强，谷氨酸通过一种新机制（AMPA受体与g蛋白偶联）抑制。我们将确定表达这种电流的神经节细胞的类型，并确定哪种视觉刺激能唤起和抑制这种电流。中央窝只占视网膜的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。了解其多个平行回路的功能结构将有助于理解视觉损伤（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。

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.