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) 为大脑提供视觉信息的唯一来源并形成建筑物 在灵长类动物中，在表征这三个方面已经取得了相当大的进展。 最常见的 RGC 类型，占视网膜输出的 80%，而对其余的知之甚少 15 种以上罕见的 RGC 类型是进展的一个关键障碍，因为在急性治疗中很难靶向这些罕见的 RGC。 通过一种可视化结构和功能的方法克服了这些挑战。 通过结合钙成像、逆行示踪剂和荧光来观察活体猕猴眼中的中心凹 RGC 自适应光学扫描光检眼镜 (FAOSLO) 成像是非侵入性的，可以进行研究。 该技术可以对相同的 RGC 群体进行数月或数年的研究，从而实现中心凹的体内分类。 RGC 识别难以捉摸的稀有类型 该提案旨在将FAOSLO 成像的能力扩展到以下领域。 直接测试这些罕见的 RGC 在视觉中的作用，同时为独立研究奠定基础 Aim One 将实施高速扫描策略和电压指示器来读取视网膜代码。 目标二：在活体眼睛中实现研究罕见的运动敏感 RGC 所需的时间分辨率。 将直接检验罕见的 ON 方向选择性 RGC 类型有助于视动眼的假设 使用单个 RGC 的靶向激光损伤进行灵长类动物的运动，目标三将建立一个范例。 分离罕见的 RGC 及其通过跨神经元逆行变性介导的视觉功能 V1 病变。该系列研究还将阐明 RGC 损失的时间线和潜在的生理学。 中风导致的 V1 损伤后 RGC 发生的变化强化了该提案的研究目标。 通过全面的培训计划，该计划将提供实现目标所需的新技能和知识 候选人的研究目标是建立稀有灵长类动物 RGC 和视觉功能之间的联系。 候选人将在 David Williams 博士的指导下进行指导阶段，David Williams 博士是使用自适应光学技术的先驱 共同导师 Bill Merigan 博士将提供行为实验、病变和病毒方面的专业知识。 来自一流咨询委员会（Krystel Huxlin 博士、Tony Movshon 和 Jesse）的额外培训 Schallek）将通过研究和培训帮助候选人走上独立之路。 拟议的将有助于候选人成功过渡到研究机构的终身教职职位 密集型大学。