Linking retinal circuits to perception

将视网膜回路与感知联系起来

• 批准号: 10330594
• 负责人: Jay Neitz
• 金额: $ 41.76万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10330594
• 关键词: Anatomy; Awareness; Behavior; Biology; Brain; Cells; Characteristics; Collection; Color; Color Perception; Color Visions; Comparative Study; Cone; Conscious; Elements; Environment; Esthesia; Event; Eye Movements; Face; Failure; Fruit; Goals; Human; Image; Light; Link; Mammals; Measures; Mediating; Modeling; Modernization; Monkeys; Movement; Nervous system structure; Neural Pathways; Neurons; Pathway interactions; Perception; Peripheral; Pharmacology; Photophobia; Physiological; Play; Positioning Attribute; Primates; Process; Pupil; Reaction; Retina; Retinal Ganglion Cells; Role; Scanning Electron Microscopy; Science; Signal Transduction; Structure; Synapses; System; Technology; Therapeutic; Time; Unconscious State; Vertebrates; Vision; Visual; Visual Pathways; Visual Perception; Visual system structure; Work; base; blind; cell type; circadian; experimental study; ganglion cell; melanopsin; neural circuit; receptive field; response; retinal prosthesis; signal processing; stem cell gene therapy; theories; visual feedback; visual information

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.

如果理论方法是提供有意义的愿景，那么我们必须调查并发现 人类感知与视觉系统中神经元和电路活性之间的联系。我们在这里提出 研究涉及主要途径的电路，作为视觉系统如何组织到的模型 发挥不同的功能。试图了解主要视觉系统的生物学的大部分努力 强调其在感知中的作用，特别是在产生外部的内部视觉表示 世界以及其中的对象和事件。但是，更原始的视觉系统的比较研究 表明愿景最初并没有发展为感知世界的系统。相反，视觉系统的视觉系统 下脊椎动物强调直接触发动作的神经回路，实时触发动作 以及提供非图像形成功能的途径，例如昼夜节律光学。我们的视觉系统有 维持进化的古老功能，这些功能并非直接参与有意识的感知。尝试 了解主要未能认识到的大部分的初级视力生物学（包括人类） 视觉系统与感知无关，限制了我们对神经通路的理解 完成视觉系统是组织的。私人中的蓝黄色粘膜理论重点是 经典的“蓝色”神经元，小型结合视网膜神经节细胞。但是，证据积累了 这些细胞可能不直接参与对蓝色和黄色色调的有意识；而是他们 非常适合触发空间定向运动。作为小型结合的想法的替代 神经节细胞是蓝黄色感觉的基础，我们发现了以前的发现 未知的电路可能仅在专门用于有意识的颜色感知的私人中演变。目标 此处提出的实验是了解如何组织主要的S-CONE途径以服务 视觉系统功能的多样性，包括非图像形成视觉功能，并且很大程度上 构建世界知觉表示与控制目标指导的动作的单独功能。 我们提出了两个具体目标： 特定目的1：确定处理来自S锥体信号的平行途径的多样性 灵长类动物视网膜使用串行块扫描电子显微镜。 特定目的2：将整个细胞和松散贴片记录的组合结合在一起 对特定突触元件的药理操纵，以直接测量空间颜色 灵长类动物视网膜中神经节细胞的接收场的组织，该电网的过程信号来自S锥体， 并将结果与​​从S-CONE途径的解剖表征获得的结果相关联。