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.

正在开发的治疗策略以恢复视力为盲人，依靠人类的刺激元素 视网膜将有50多种不同类型的神经元组织成专业电路，其中一些电路 调解有意识的感知，而其他人则提供非成像形成功能，例如昼夜节律 光座和引导运动运动。但是，几乎没有达成共识 超过20个神经节细胞类型负责特定的视觉功能。同样，关于 视网膜电路为人类感知经验以外的各种任务做出了贡献。这些代表 必须填补的知识基本差距，以提供必要的信息来指导努力来保存 或还原视觉功能，例如对象识别而不会无意间干扰必需的非图像 - 形成功能。因此，这里提出的工作的长期目标是通过 在两个关键问题上取得了切实的进步。 首先，看到和识别对象的能力需要多样化的细胞，载有不同信息 参与有意识的特定大脑区域。例如，对象的形状和边界 视觉场景由黑色，白色，灰色阴影和颜色的感知表示。具体目标1是 检验以前在内部和外部未批准的侏儒电路特征的假设 丛状层，执行负责颜色和黑白视觉的初始计算，然后 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，每种都与信号表面反射率有关，而不是 仅视网膜图像中光的光谱特性。 第二，使用串行块面扫描电子显微镜（SBFSEM）进行灵长类动物视网膜的3D重建 揭示了带有短波长的视网膜神经节细胞类型的意外多样性和数量 锥信号。 S-Cone Connectome包括冗余颜色编码神经节细胞，这些细胞投射到许多 大脑区域除了有意识的彩色视觉外，还为广泛的功能提供相同的颜色信息。 特定目标2是要完全了解携带S-Cone的所有类型的视网膜神经节细胞 灵长类动物视网膜中的信号，负责其响应特征的电路以及每个扮演的作用 指导我们的行为。这将使用SBFSEM和单细胞电生理学完成。