Functional Imaging of Retinal Ganglion Cells Receiving S-cone Inputs Using Viral-Delivered ArcLight A242

使用病毒传播的 ArcLight A242 接收 S 锥体输入的视网膜神经节细胞的功能成像

• 批准号: 8835861
• 负责人: Adam Crain
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-08 至 2017-12-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8835861
• 关键词: Acids; Agonist; Appearance; Behavior; Biological; Biosensor; Cell Therapy; Cell model; Cells; Characteristics; Chemicals; Circadian Rhythms; Color; Color Perception; Color Visions; Cone; Conscious; Custom; Data; Feedback; Fluorescence; Functional Imaging; GRM6 gene; Ganglia; Gene Delivery; Genetic; Glutamate Receptor; Goals; Human; Individual; Inherited; Label; Measures; Mediating; Metabotropic Glutamate Receptors; Modeling; Mus; Mutation; Neurologic; Neurons; Output; Pathway interactions; Perception; Physiological; Physiology; Play; Primates; Process; Property; Retina; Retinal; Retinal Ganglion Cells; Role; Signal Transduction; Staging; Stimulus; Sum; System; Testing; Therapeutic; Unconscious State; Viral; Vision; Visual system structure; Work; area MT; base; blind; color processing; experience; ganglion cell; gene therapy; horizontal cell; koniocellular; melanopsin; nonhuman primate; public health relevance; research study; response; retinal neuron; retinal prosthesis; success; theories; visual stimulus

DESCRIPTION (provided by applicant): Technological advances in gene and cell therapies, retinal prostheses, and chemical photoswitches all show promise for restoring sight to the blind; however an accurate understanding of the functional role of each of the different types of retinal ganglion cells (RGCs) in human behavior is key to realizing the potential for these therapeutic approaches. The long-term goal of the Neitz labs is to understand all the circuitry responsible for human vision using the non-human primate as a model. As a step toward achieving that goal, this proposal focuses on the circuitry involving RGCs that receive input from short wavelength (S) cones. Color vision has served as a premier example of a success in understanding the biological underpinnings of perception. While the characteristics of the cones and the spectral sensitivities of the photopigments and their importance for trichromatic color vision are understood in detail, understanding of how the outputs of the cones are processed to give rise to perceptions is still far from complete. The S-cone pathways play a role in the conscious perception of all hues and supply retinal ganglion cells (RGCs) with important information regarding color for circadian rhythms. Based on the long known discrepancies between primate retinal physiology and human color perception, and on new data from the Neitz lab, the Neitz's hypothesize that S-cone input to hue perception is present both in the blue-yellow and red-green systems. The model makes specific predictions regarding the activities in midget ganglion cells in response to selective activation of S cones, including that midget ganglion cells receiving S cone input would not respond to white-dark edges and in this manner would differ from the conventional L vs. M midget ganglion cells that do respond well to white-dark boundaries. To test predictions of this model, I propose the following specific aim: Specific Aim 1: Optically record and analyze the activity of RGCs receiving S cone input in primate retina by using the biosensor ArcLight introduced by viral mediated gene delivery. The complete circuitry for processing S cone signals will be worked out using a custom visual stimulus to activate only S cones. ArcLight labeled neurons receiving S cone input will change in fluorescence intensity.

描述（由申请人提供）：基因和细胞疗法、视网膜假体和化学光开关方面的技术进步都显示出恢复盲人视力的希望；然而，准确了解每种不同类型的视网膜神经节细胞 (RGC) 在人类行为中的功能作用是实现这些治疗方法潜力的关键。 Neitz 实验室的长期目标是了解负责的所有电路 使用非人类灵长类动物作为模型的人类视觉。作为实现这一目标的一步，该提案重点关注涉及从短波长 (S) 锥体接收输入的 RGC 的电路。色觉是成功理解感知的生物学基础的首要例子。虽然我们详细了解了视锥细胞的特性和感光色素的光谱敏感性及其对三色视觉的重要性，但对如何处理视锥细胞的输出以产生感知的了解还远未完成。 S 锥体通路在所有颜色的意识感知中发挥着重要作用，并为视网膜神经节细胞 (RGC) 提供有关昼夜节律颜色的重要信息。基于长期以来已知的灵长类动物视网膜生理学和人类色彩感知之间的差异，以及 Neitz 实验室的新数据，Neitz 假设 S 锥体对色调感知的输入同时存在于蓝黄系统和红绿系统中。该模型针对小型神经节细胞响应 S 锥体选择性激活的活动做出具体预测，包括接收 S 锥体输入的小型神经节细胞不会对白暗边缘做出反应，因此与传统的 L 与 M 侏儒神经节细胞不同，后者对白暗边界有良好的反应。为了测试该模型的预测，我提出以下具体目标： 具体目标 1：通过使用病毒介导的基因传递引入的生物传感器 ArcLight，光学记录和分析灵长类动物视网膜中接收 S 锥体输入的 RGC 的活动。用于处理 S 锥体信号的完整电路将使用自定义视觉刺激来仅激活 S 锥体来设计。 ArcLight 标记的神经元接收 S 锥体输入后荧光强度会发生变化。