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.

摘要 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 所有下游视觉的块。在灵长类动物中， 最常见的RGC类型，占视网膜输出的80%，其余的则知之甚少。 15+稀有RGC类型。进展的一个关键障碍是难以在急性炎症中靶向这些罕见的RGC。 实验这些挑战已经克服了可视化的结构和功能的方法 应用钙离子成像、逆行示踪和荧光技术研究猕猴视网膜神经节细胞 自适应光学扫描光检眼镜（FAOSLO）。FAOSLO成像是非侵入性的， 几个月或几年的同一个RGC人口。这项技术已经能够在体内分类的中心凹 RGC用于识别难以捉摸的罕见类型。该提案旨在扩大FAOSLO成像的能力， 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 事业Aim One将实现高速扫描策略和电压指示器来读取视网膜代码 在活体眼睛中，并达到研究罕见的运动敏感RGC所需的时间分辨率。目标二 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 运动的灵长类动物使用有针对性的激光损伤个别RGCs。目标三将建立一个范例， 分离罕见的RGC和它们通过跨神经元逆行变性介导的视觉功能， V1病变。这条调查线还将阐明RGC损失的时间轴和潜在的生理学变化。 中风时V1受损后RGCs发生的变化。这一建议的研究目标得到加强 一个全面的培训计划，将提供必要的新技能和知识，以实现 候选人的研究目标是建立罕见的灵长类动物RGCs和视觉功能之间的联系。的 候选人将与大卫威廉姆斯博士一起进行指导阶段，他是自适应光学用于 对眼睛进行成像。共同导师比尔·梅里根博士将贡献行为实验，病变和病毒 向量。一流咨询委员会（Krystel Huxlin博士、Tony Movshon博士和Jesse博士）提供的额外培训 沙莱克）将使候选人走上一条通往独立的强有力的道路。在一起，研究和培训 建议将促进候选人的成功过渡到终身教职职位的研究- 密集型大学