Genetic Manipulation of Retinal Ganglion Cell Subtypes

视网膜神经节细胞亚型的基因操作

• 批准号: 10688275
• 负责人: Tiffany M. Schmidt
• 金额: $ 20万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10688275
• 关键词: Ablation; Address; Animal Behavior; Animals; Arousal; Behavior; Behavioral; Brain; Brain region; Candidate Disease Gene; Cell Culture Techniques; Cell physiology; Cells; Communities; Complement; Conscious; Contrast Sensitivity; Custom; Data; Development; Dyes; Exploratory/Developmental Grant; Fluorescent in Situ Hybridization; Future; Gene Expression; Generations; Genes; Genetic; Genetic Markers; Goals; Health; Hormones; Human; Immunohistochemistry; Individual; Investments; Label; Learning; Light; Link; Maps; Mental Health; Miosis disorder; Modeling; Modernization; Molecular; Moods; Morphology; Mus; Neurons; Neurosciences; Organism; Output; Physiological; Physiology; Population; Property; Reagent; Research Personnel; Resolution; Retina; Retinal Ganglion Cells; Role; Scheme; Specificity; Stimulus; Subconscious; System; Time; Validation; Viral Vector; Visual; Visual Fields; Visual Perception; Visual System; adeno-associated viral vector; candidate identification; candidate validation; cell type; circadian; experience; frontier; genetic manipulation; insight; melanopsin; molecular marker; physical conditioning; response; sensory system; tool; transcriptome sequencing; visual neuroscience; visual stimulus

PROJECT SUMMARY Light is a profoundly important regulator of physiology and behavior across a wide range of organisms. Light information is relayed via diverse retinal ganglion cell types to approximately 50 distinct targets in the brain. The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent 6 of the 40 retinal ganglion cell types present in the mouse retina. The M1-M6 ipRGC subtypes each possess a distinct complement of morphological and physiological features, central projections, and behavioral roles. Thus, mapping of ipRGC circuits with single subtype resolution would provide critical insight into the function of multiple and varied visual circuits. However, progress on this front has been hampered by a dearth of genetic tools for label, manipulation, and ablation of single subtypes of retinal ganglion cell. Our preliminary data indicate that a Cre and Flp-based intersectional approach could allow for such manipulation of single ipRGC subtypes. This proposal aims to identify genetic marker combinations unique to single ipRGC subtypes. Additionally, we will simultaneously create a modular genetic toolkit that can be integrated into any Cre/Flp motif for future ipRGC subtype manipulation. These tools will not only provide immediate insight into ipRGC-connected circuits, but will provide critical tools and an experimental pipeline for the visual and circuit neuroscience communities to study a broad range of circuits to link cellular function to behavior.

项目概要 光是多种生物体生理和行为的极其重要的调节剂。光 信息通过不同类型的视网膜神经节细胞传递到大脑中大约 50 个不同的目标。这 表达黑视蛋白、本质上感光的视网膜神经节细胞 (ipRGC) 代表 40 个视网膜中的 6 个 小鼠视网膜中存在的神经节细胞类型。 M1-M6 ipRGC 亚型各自具有独特的补体 形态和生理特征、中心预测和行为角色。因此，ipRGC 的映射 具有单一亚型分辨率的电路将为多种不同视觉功能提供重要的见解 电路。然而，由于缺乏用于标记、操作、 以及视网膜神经节细胞单一亚型的消融。我们的初步数据表明基于 Cre 和 Flp 的 交叉方法可以允许对单个 ipRGC 亚型进行此类操作。该提案旨在 识别单个 ipRGC 亚型特有的遗传标记组合。另外，我们将同时 创建一个模块化遗传工具包，可以集成到未来 ipRGC 亚型的任何 Cre/Flp 基序中 操纵。这些工具不仅可以立即洞察 ipRGC 连接的电路，而且可以提供 视觉和电路神经科学界研究广泛的关键工具和实验管道 将细胞功能与行为联系起来的一系列电路。