STRUCTURE AND FUNCTION OF PARALLEL CHANNELS IN THE FOVE

我们的主要目标是了解连接中心凹锥体和神经节细胞的回路。本时期的结构研究表明，中央凹有多个神经节细胞阵列。我们建议每个阵列表示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=遮阳伞(M)细胞；高时间频率=花环细胞(M)；色调=蓝黄细胞、红绿细胞。我们现在计划阐明EM文库中剩余神经节细胞的电路，从而确定从中心凹到脑的所有平行通道。我们还计划通过识别突触的功能成像来检验这些假设：用过氧化物酶示踪剂孵育视网膜，并简要呈现一种特定的时空颜色模式来激发胞吐作用。当融合的突触小泡被内吞作用取回时，它们隔离固定的示踪剂，然后用共聚焦和电子显微镜观察。不同类型的双极突触和无长突突触中标记的小泡的比率衡量了它们对给定刺激的相对释放。这种方法现在正在为豚鼠视网膜的颜色对抗回路而开发，将被应用于灵长类视网膜的同源回路。最后，我们计划确定cGMP门控通道如何参与神经节细胞S的视觉反应。通过一种新的机制(AMPA受体与G蛋白偶联)，一氧化氮增强该通道的电流，而谷氨酸则抑制该通道的电流。我们将确定表达这种电流的神经节细胞的类型，并确定哪些视觉刺激可以激发和抑制这种电流。中心凹只占视网膜的2mm2(0.3%)，但它提供一半的视觉皮质，因此是人类视觉的关键。了解其多个平行回路的功能架构将有助于理解视觉损害(如黄斑水肿和老年性黄斑变性)，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.