Linking retinal circuits to perception

将视网膜回路与感知联系起来

• 批准号: 10582376
• 负责人: Jay Neitz
• 金额: $ 57.69万
• 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 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582376
• 关键词: 3-Dimensional; Agreement; Area; Behavior; Biological; Brain; Cells; Characteristics; Code; Color; Color Visions; Computer software; Cone; Conscious; Data; Development; Electron Microscopy; Electrophysiology (science); Elements; Equilibrium; Esthesia; Eye Movements; Face; Hand; Human; Image; Individual; Inner Plexiform Layer; Investigation; Knowledge; Light; Link; Macaca; Mediating; Motor; Movement; Neurons; Outcome; Output; Pathway interactions; Perception; Photophobia; Play; Primates; Property; Protocols documentation; Publishing; Resolution; Retina; Retinal Ganglion Cells; Role; Sample Size; Scanning Electron Microscopy; Shapes; Signal Transduction; Sum; Surface; Synapses; Technology; Testing; Therapeutic; Therapeutic Intervention; Tissues; Vision; Visual; Visual Pathways; Visual Perception; Work; blind; cell type; circadian; connectome; detector; experience; ganglion cell; light microscopy; object recognition; outer plexiform layer; preservation; reconstruction; response; retinal imaging; retinal neuron; retinal prosthesis; sight for the blind; sight restoration; stem cell gene therapy; therapeutically effective; tissue preparation

Therapeutic tactics under development to restore sight to the blind rely on stimulating elements in the human retina where more than 50 different types of neuron are organized into specialized circuits, some of which mediate conscious perception, while others serve non-imaging forming functions, such as circadian photoentrainment and guiding motor movements. However, there is little agreement about which of the more than 20 ganglion cell types are responsible for specific visual functions. Similarly, little is understood about the retinal circuits contributing to the diverse tasks outside the human perceptual experience. These represent fundamental gaps in knowledge that must be filled to provide information necessary to guide efforts to preserve or restore visual functions such as object recognition without inadvertently interfering with essential non-image- forming functions. Thus, the long-term objective of the work proposed here is to fill these gaps in knowledge by making tangible progress on two key issues. First, the ability to see and recognize objects requires a diversity of cells carrying different information to specific brain areas involved in conscious vision. For example, the shapes and boundaries of objects in a visual scene are represented by the percepts of black, white, shades of gray, and color. Specific Aim 1 is to test the hypothesis that previously unappreciated features of the midget circuitry, both in the inner and outer plexiform layers, carry out the initial computations responsible for color and black and white vision, and that this is done by circuitry that separates midget ganglion cells into six types corresponding to the sensations of red, green, blue, yellow, black, and white, each of which are associated with signaling surface reflectance, not merely the spectral properties of light in the retinal image. Second, 3D reconstructions of primate retina using serial block face scanning electron microscopy (SBFSEM) have revealed an unexpected diversity and quantity of retinal ganglion cell types carrying short-wavelength (S) cone signals. The S-cone connectome includes redundant color-coding ganglion cells that project to many brain areas providing the same color information for a broad range of functions besides conscious color vision. Specific Aim 2 is to gain a complete understanding of all the types of retinal ganglion cells carrying S-cone signals in the primate retina, the circuitry responsible for their response characteristics, and the role each plays in guiding our behaviors. This will be done using SBFSEM and single-cell electrophysiology.

正在开发的恢复盲人视力的治疗策略依赖于人体内的刺激元素， 视网膜，其中有50多种不同类型的神经元组成专门的回路，其中一些 介导有意识的感知，而其他服务非成像形成功能，如昼夜节律 光诱导和引导电机运动。然而，关于哪一个更重要， 超过20种神经节细胞负责特定的视觉功能。同样，人们对 视网膜回路有助于人类感知经验之外的各种任务。这些代表 必须填补知识方面的根本空白，以提供必要的信息，指导保护工作， 或恢复视觉功能，如物体识别，而不会无意中干扰基本的非图像， 形成功能。因此，这里提出的工作的长期目标是通过以下方式填补这些知识空白： 在两个关键问题上取得切实进展。 首先，要具备看到和识别物体的能力，需要携带不同信息的细胞的多样性， 参与有意识视觉的特定大脑区域。例如， 视觉场景由黑色、白色、灰色阴影和颜色的感知来表示。具体目标1是 测试的假设，以前未被赞赏的功能侏儒电路，无论是在内部和外部 丛状层，执行负责颜色和黑色和白色视觉的初始计算， 这是通过将侏儒神经节细胞分为六种类型的电路来完成的， 红色、绿色、蓝色、黄色、黑色和白色，其中的每一个与信号表面反射率相关联，而不是 仅仅是视网膜图像中光的光谱特性。 第二，使用连续块面扫描电子显微镜（SBFSEM）进行灵长类动物视网膜的3D重建 已经揭示了携带短波长（S）的视网膜神经节细胞类型的意外多样性和数量， 锥体信号。S锥连接体包括冗余的颜色编码神经节细胞， 除了有意识的颜色视觉之外，大脑区域还为广泛的功能提供相同的颜色信息。 具体目标2是获得对所有类型的视网膜神经节细胞携带的S-锥的完整理解， 灵长类动物视网膜中的信号，负责其响应特性的电路，以及每个信号所扮演的角色 来指导我们的行为。这将使用SBFSEM和单细胞电生理学完成。