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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：
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
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/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

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.

项目总结