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-锥体通路的回路，作为视觉系统如何组织的模型， 服务于不同的功能。在试图了解灵长类动物视觉系统的生物学方面， 强调了它在感知中的作用，特别是在产生外部的内部视觉表示方面 世界以及其中的物体和事件。然而，比较研究更原始的视觉系统， 表明视觉最初并不是作为一种感知世界系统而进化的。相反， 低等脊椎动物强调直接触发动作的神经回路，即时，在真实的时间 以及用于非成像功能如昼夜光诱导的途径。我们的视觉系统 保持着进化上古老的功能，这些功能并不直接参与意识感知。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认识到大部分的视觉功能。 视觉系统与感知无关限制了我们对神经通路的理解 包括视觉系统。关于灵长类动物蓝黄色视觉的理论主要集中在 典型的“蓝色开启”神经元，即小型双层视网膜神经节细胞。然而，有证据表明， 这些细胞可能并不直接参与对蓝色和黄色色调的有意识感知;相反，它们 非常适合于触发空间定向运动。作为小双分层理论的替代 神经节细胞是蓝黄色感觉的基础，我们已经发现，以前 这种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 这里提出的实验是为了了解灵长类动物的S-锥通路是如何组织的， 视觉系统功能的多样性，包括非图像形成视觉功能， 构建世界的感知表征与控制目标导向的行动的独立功能。 我们提出两个具体目标： 具体目标1：研究大脑皮层中S视锥细胞信号处理的平行通路的多样性。 灵长类动物视网膜使用连续块面扫描电子显微镜。 具体目标2：使用全细胞和松散贴片记录的组合， 药理学操作特定的突触元件，以直接测量空间色性 灵长类视网膜中处理来自S视锥的信号的神经节细胞的感受野的组织， 并将结果与从S-视锥通路的解剖学表征获得的结果相关联。