Linking retinal circuits to perception

如果治疗方法要提供有意义的愿景，我们必须调查和发现 人类感知与视觉系统中神经元和回路的活动之间的联系。在这里，我们建议 研究灵长类动物中涉及S视锥通路的回路，以此作为视觉系统如何组织的模型 服务功能多样。在试图了解灵长类视觉系统的生物学方面所做的大量努力 强调它在感知方面的作用，特别是在产生外部的内部视觉表现方面 世界以及其中的对象和事件。然而，对更原始的视觉系统的比较研究 这表明视觉最初并不是作为一种感知世界的系统而发展起来的。相反，人类的视觉系统 低等脊椎动物强调直接触发运动的神经回路，每时每刻，实时地 以及用于非成像功能的路径，例如昼夜光夹带。我们的视觉系统有 维持着进化上古老的功能，这些功能并不直接与意识感知有关。试图 了解灵长类动物(包括人类)的视觉生物学，这些灵长类动物未能识别出大部分 视觉系统不关心知觉，限制了我们对神经通路的了解 包括视觉系统的数据被组织起来。灵长类动物蓝黄色视觉的理论主要集中在 经典的“蓝光”神经元，小的双层视网膜神经节细胞。然而，证据已经积累起来 这些细胞可能不直接参与对蓝色和黄色的有意识感知；相反，它们 非常适合于触发空间定向运动。作为一种替代小型双层结构的想法 神经节细胞是蓝黄色感觉的基础，我们的发现指向了之前 未知的回路可能只在灵长类动物中进化出来，专门用于有意识的颜色感知。目标是 这里提出的实验之一是为了了解灵长类动物中S-锥体通路是如何组织起来的 视觉系统功能的多样性，包括非成像的视觉功能和大量的 构建对世界的知觉表征与控制目标导向的行动的不同功能。 我们提出两个具体目标： 具体目标1：计算处理S视锥信号的并行路径的多样性 灵长类视网膜连续区块面部扫描电子显微镜观察 具体目标2：结合使用全细胞和松散斑片记录 直接测量空间色调的特定突触元件的药理学操作 灵长类动物视网膜中处理S视锥细胞信号的神经节细胞感受野的组织， 并将这些结果与S-锥体径路的解剖学特征相关联。

If therapeutic approaches are to provide meaningful vision, it is essential that we investigate and discover the links between human perception and the activity of neurons and circuits in the visual system. Here we propose to study circuits involving S-cone pathways in primates as a model for how the visual system is organized to serve diverse functions. Much of the effort in trying to understand the biology of the primate visual system has emphasized its role in perception, in particular with producing an internal visual representation of the outside world and the objects and events within it. However, comparative studies of more primitive visual systems indicate that vision did not originally evolve as a system for perceiving the world. Rather, the visual systems of lower vertebrates emphasize neural circuitry for directly triggering movements, moment-to-moment, in real time and pathways serving non-image forming functions such as circadian photoentrainment. Our visual system has maintained evolutionarily ancient functions that are not directly involved in conscious perception. Attempts to understand the biology of vision in primates (including humans) that have failed to recognize that much of the visual system is not concerned with perception have limited our understanding of how the neural pathways comprising the visual system are organized. Theories of blue-yellow color vison in primates have focused on the classic “blue-ON” neuron, the small bistratified retinal ganglion cell. However, evidence has accumulated that these cells may not be directly involved in the conscious perception of blue and yellow hues; rather they are well suited for triggering spatially directed movements. As an alternative to the idea that small bistratified ganglion cells are the basis for blue-yellow sensations, we have made discoveries that point to previously unknown circuitry that may have evolved only in primates specifically for conscious color perception. The goal of the experiments proposed here is to understand how S-cone pathways in primates are organized to serve the diversity of functions of the visual system including non-image forming vision functions and the largely separate functions of constructing a perceptual representation of the world vs. controlling goal-directed actions. We propose two specific aims: Specific Aim 1: To work out the diversity of parallel pathways for processing of signals from S cones in the primate retina using Serial Block Face Scanning Electron Microscopy. Specific Aim 2: To use a combination of whole-cell and loose patch recording in combination with pharmacological manipulation of specific synaptic elements to directly measure the spatio-chromatic organization of the receptive fields of ganglion cells in the primate retina that process signals from S cones, and to correlate the results to those obtained from anatomical characterization of S-cone pathways.