Neurophysiology of the Fovea

中央凹的神经生理学

• 批准号: 10002243
• 负责人: Michael Tri Hoang Do
• 金额: $ 44.25万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002243
• 关键词: Accounting; Acute; Address; Anatomy; Attention; Awareness; Axon; Benchmarking; Biological; Biophysical Process; Blindness; Cell physiology; Cells; Characteristics; Clinical Treatment; Complement; Computer Models; Cone; Conscious; Contrast Sensitivity; Data; Data Set; Dependence; Diagnosis; Eagles; Electrophysiology (science); Eye; Eye Movements; Face; Feedback; Frequencies; Genome; Health; Human; Image; Individual; Ion Channel Gating; Kinetics; Knowledge; Light; Macaca; Macular degeneration; Measures; Membrane; Methods; Modeling; Mus; Muscle Cells; Nature; Neurons; Noise; Optics; Output; Performance; Peripheral; Pharmacology; Photons; Phototransduction; Physiology; Play; Positioning Attribute; Presynaptic Terminals; Primates; Property; Publications; Publishing; Reading; Resolution; Retina; Retinal Cone; Retinal Ganglion Cells; Role; Sensory; Shapes; Signal Transduction; Stimulus; Structure; Testing; Tissues; Vertebrate Photoreceptors; Vision; Visual; Visual Acuity; Work; absorption; biological systems; experimental study; fovea centralis; improved; insight; macula; neuronal cell body; neurophysiology; patch clamp; peer; preservation; response; single-cell RNA sequencing; statistics; visual performance; visual stimulus; voltage; voltage clamp

Most conscious vision in humans and other primates begins with the fovea, a specialization of the central retina that encodes the image in exceptional detail. The cone photoreceptors of the fovea are tailored for high spatial acuity. They have a tiny cross-section and dense packing, allowing them to form an extremely fine pixel array. Foveal cones also extend long axons that allow downstream cells to be displaced laterally from the light path, providing direct access to the visual image. Each of the principal output neurons of the fovea—the midget retinal ganglion cells (RGCs)—is also driven by a single cone, preserving spatial resolution. By contrast, cones of the peripheral retina are broad, widely spaced, and positioned behind layers of cell bodies and processes; additionally, more than a dozen peripheral cones converge upon single midget RGCs, further reducing spatial resolution. These anatomical specializations of the fovea have been recognized for decades. The overarching hypothesis of this proposal is that foveal cones also possess functional specializations for high-acuity vision. Indeed, a recent publication has indicated that phototransduction is more prolonged in foveal than peripheral cones. The consequences of this distinction are not yet clear. Much depends on how the light responses of foveal cones are shaped downstream of phototransduction, by voltage-gated ion channels (VGICs). Experiments proposed in Aim 1 test the hypothesis that VGICs complement the distinct kinetics of foveal phototransduction. The ability to encode fine spatial detail also depends on the signal/noise ratio. Achieving high signal/noise would appear especially important for foveal cones, which have little opportunity to pool their signals to improve the response fidelity of foveal midget RGCs. In Aim 2, we test the hypothesis that the signal/noise of foveal cones is increased at multiple stages, including the currents produced by phototransduction and VGICs as well as their effect on the membrane voltage at the soma and synaptic terminal. For both aims, our principal approach is to apply patch-clamp electrophysiology to foveal and peripheral cones that are embedded within retinal circuitry or have been acutely dispersed into single cells. These experiments are complemented by computational modeling. We maintain an experimental platform that supplies us with foveal and peripheral tissue for quantitative analysis. The work proposed here constitutes early steps toward a full understanding of the fovea at the level of cellular neurophysiology.

人类和其他灵长类动物的大多数有意识的视觉都始于中央凹，这是中央凹的一种特化。 视网膜对图像进行特殊细节的编码。视网膜中央凹的视锥光感受器是为高 空间敏锐度它们有一个微小的横截面和密集的包装，使他们能够形成一个极其精细的像素 阵中央凹视锥还延伸长轴突，允许下游细胞因光线而侧向移位 路径，提供对视觉图像的直接访问。中央凹的每个主要输出神经元-侏儒 视网膜神经节细胞（RGC）-也由单个锥体驱动，保持空间分辨率。相比之下， 周边视网膜是广泛的，广泛的间距，并位于细胞体和过程层的后面; 此外，十几个周边锥体聚集在单个侏儒RGC上，进一步减少了空间 分辨率视网膜中央凹的这些解剖学特化已经被认识了几十年。总体 该建议的假设是中央凹视锥也具有用于高敏锐度视觉的功能特化。 事实上，最近的出版物表明，光转导是更长的中央凹比周边 圆锥体。这种区分的后果尚不清楚。这在很大程度上取决于 中央凹视锥通过电压门控离子通道（VGIC）在光转导的下游成形。 目的1中提出的实验检验了VGIC补充了中央凹的不同动力学的假设。 光传导对精细空间细节进行编码的能力还取决于信噪比。实现 高信号/噪声对于中央凹视锥将显得特别重要，中央凹视锥几乎没有机会汇集它们的 信号，以提高反应保真度的中央凹侏儒RGC。在目标2中，我们测试了假设， 中央凹视锥的信号/噪声在多个阶段增加，包括 以及它们对索马和突触膜电压的影响 终端对于这两个目标，我们的主要方法是将膜片钳电生理学应用于中央凹和 周边视锥细胞嵌入视网膜回路内或已急剧分散成单个细胞。 这些实验是由计算机建模的补充。我们有一个实验平台 为我们提供了用于定量分析的中央凹和周边组织。这里提出的工作包括： 在细胞神经生理学的水平上对中央凹的全面理解的早期步骤。