Linking rare primate ganglion cells to downstream visual functions

将稀有灵长类神经节细胞与下游视觉功能联系起来

• 批准号: 10721221
• 负责人: Sara S Patterson
• 金额: $ 13.35万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10721221
• 关键词: Ablation; Action Potentials; Acute; Advisory Committees; Amacrine Cells; Area; Behavior; Behavioral; Blindness; Brain; Calcium; Cell Communication; Cell physiology; Classification; Code; Conscious; Cortical Blindness; Detection; Disease; Electrophysiology (science); Eye; Eye Movements; Faculty; Feedback; Fluorescence; Foundations; Goals; Health; Image; Imaging Techniques; Individual; Investigation; Knowledge; Lasers; Lesion; Light; Link; Longitudinal Studies; Macaca; Measures; Mediating; Mentors; Modeling; Motion; Neurons; Ophthalmoscopy; Optokinetic nystagmus; Output; Pathway interactions; Patients; Phase; Physiological; Physiology; Population; Positioning Attribute; Primates; Property; Reflex action; Research; Resolution; Retina; Retinal Degeneration; Retinal Ganglion Cells; Retrograde Degeneration; Role; Scanning; Signal Transduction; Source; Speed; Standard Model; Stroke; Structure; Technical Expertise; Techniques; Testing; Tracer; Training; Trans-Synaptic Degeneration; Universities; Viral Vector; Vision; Visual; Visual Cortex; Visual Pathways; Visual Perception; Visual System; Visual impairment; Visualization; adaptive optics; blind; career; cell type; experimental study; ganglion cell; improved; in vivo; in vivo calcium imaging; neural; optical imaging; preservation; response; skills; temporal measurement; tenure track; timeline; tool; transmission process; visual information; visual neuroscience; visual processing; voltage

ABSTRACT Retinal ganglion cells (RGCs) provide the sole source of visual information to the brain and form the building blocks for all downstream vision. In primates, considerable progress has been made in characterizing the three most common RGC types, which make up 80% of the retinal output, and much less is known about the remaining 15+ rarer RGC types. A key barrier to progress has been the difficulty of targeting these rare RGCs in acute experiments. These challenges have been overcome with an approach for visualizing the structure and function of foveal RGCs in the living macaque eye by combining calcium imaging, retrograde tracers and fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO). FAOSLO imaging is non-invasive and enables study of the same RGC populations for months or years. This technique has enabled in vivo classification of foveal RGCs to identify the elusive rarer types. This proposal aims to extend the capabilities of FAOSLO imaging to directly test the roles of these rare RGCs in vision while establishing the foundation for an independent research career. Aim One will implement high-speed scanning strategies and voltage indicators to read the retinal code in the living eye and achieve the temporal resolution necessary to study rare motion-sensitive RGCs. Aim Two will directly test the hypothesis that the rare ON direction selective RGC type contributes to optokinetic eye movements in primates using targeted laser lesions of individual RGCs. Aim Three will establish a paradigm to isolate rare RGCs and the visual functions they mediate through transneuronal retrograde degeneration following V1 lesions. This line of investigation will also clarify the timeline of RGC loss and the underlying physiological changes that occur in RGCs following V1 damage in strokes. The research goals of this proposal are reinforced by a comprehensive training plan that will provide the new skills and knowledge necessary to achieve the candidate’s research goal of establishing the links between rare primate RGCs and visual functions. The candidate will carry out the mentored phase with Dr. David Williams, a pioneer in the use of adaptive optics for imaging the eye. Co-mentor Dr. Bill Merigan will contribute expertise in behavioral experiments, lesions and viral vectors. Additional training from a first-rate advisory committee (Drs. Krystel Huxlin, Tony Movshon and Jesse Schallek) will put the candidate on a strong pathway to independence. Together, the research and training proposed will facilitate the candidate’s successful transition to a tenure-track faculty position at a research- intensive university.

抽象的 视网膜神经节细胞（RGC）为大脑提供了唯一的视觉信息来源，并形成建筑物 所有下游视觉的块。在私人中，在表征这三个方面取得了很大进展 最常见的RGC类型，占剩余输出的80％，剩余的少得多 15多个稀有RGC类型。进步的关键障碍是在急性中瞄准这些稀有RGC的困难 实验。这些挑战已经通过可视化结构和功能的方法来克服 通过结合钙成像，逆行示踪剂和荧光，在活猕猴眼中的中央凹RGC 自适应光学扫描光眼镜检查（Faoslo）。 Faoslo成像是无创的，可实现研究 数月或数年的相同RGC人群中。该技术已实现了动脉凹的体内分类 RGC识别难以捉摸的稀有类型。该建议旨在将Faoslo成像的能力扩展到 直接测试这些罕见RGC在视觉中的作用，同时为独立研究建立基础 职业。 AIM ONE将实施高速扫描策略和电压指标来读取剩余代码 在活眼睛中，并实现研究稀有运动敏感RGC所需的临时分辨率。瞄准两个 将直接检验以下假设：罕见在方向上选择性RGC类型有助于光动量 使用单个RGC的靶向激光病变中的主运动。目标三将建立一个范式 分离出稀有的RGC及其通过跨神经元逆行变性所介导的视觉功能 V1病变。这种调查线还将阐明RGC损失的时间表和基本的生理学 v1损害中风后RGC发生的变化。该提案的研究目标得到了加强 通过一项全面的培训计划，该计划将提供实现必要的新技能和知识 候选人的研究目标是建立稀有灵长类动物RGC与视觉功能之间的联系。这 候选人将与David Williams博士一起进行此事阶段，David Williams博士是使用自适应光学器件的先驱 成像眼睛。 Co-Merigan博士将在行为实验，病变和病毒方面贡献专业知识 向量。一流咨询委员会的额外培训（Krystel Huxlin博士，Tony Movshon和Jesse Schallek）将使候选人走上强大的独立途径。一起研究和培训 拟议的将促进候选人的成功过渡到研究的终身教师职位 - 密集大学。