Genetic Manipulation of Retinal Ganglion Cell Subtypes

视网膜神经节细胞亚型的基因操作

基本信息

批准号：
10528207
负责人：
Tiffany M. Schmidt
金额：
$ 24万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
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/10528207
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 Modeling Modernization Molecular Moods Morphology Mus Neurons Neurosciences Organism Output Photosensitivity Physiological Physiology Population Property Pupil 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 structure adeno-associated viral vector base cell type circadian constriction experience frontier genetic manipulation insight melanopsin molecular marker physical conditioning response sensory system tool transcriptome sequencing visual neuroscience visual stimulus

项目摘要

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.

项目摘要光是广泛生物体的生理和行为的非常重要的调节剂。光通过各种视网膜神经节细胞类型将信息传达到大脑中的大约50个不同的靶标。这表达黑素的，本质上光敏性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子类型每个都有独特的补充形态学和生理特征，中央预测和行为角色。因此，IPRGC的映射单个亚型分辨率的电路将提供对多种视觉和各种视觉的功能的关键见解电路。然而，这方面的进展受到了缺乏标签，操纵，视网膜神经节细胞的单个亚型的消融。我们的初步数据表明基于CRE和FLP 交叉方法可以操纵单个IPRGC亚型。该建议旨在识别单个IPRGC亚型独有的遗传标记组合。另外，我们将同时创建一个模块化遗传工具包，该工具包可以集成到任何CRE/FLP图案中以供将来的IPRGC亚型操纵。这些工具不仅可以立即洞悉IPRGC连接电路，还将提供关键工具和视觉和电路神经科学群落的实验管道，以研究广泛电路范围将蜂窝函数与行为联系起来。