Mechanisms underlying orientation selectivity in the mature mouse retina

成熟小鼠视网膜方向选择性的潜在机制

• 批准号: 9894639
• 负责人: Hector Acaron
• 金额: $ 3.29万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894639
• 关键词: Action Potentials; Address; Algorithms; Animal Behavior; Animals; Axon; Behavior; Biological Models; Brain; Brain region; Calcium; Cells; Data; Detection; Development; Disease; Dorsal; Electrophysiology (science); Environment; Eye; Fire - disasters; GABA-A Receptor; Goals; Grant; Health; Image; Injections; Knowledge; Label; Lateral Geniculate Body; Learning; Link; Measures; Mediating; Molecular; Morphology; Mus; Neurons; Neurosciences; Organism; Pathway interactions; Pattern; Pharmacology; Population; Process; Property; Reporting; Retina; Retinal Ganglion Cells; Sensory; Shapes; Signal Transduction; Stimulus; Structure; Synapses; Testing; Time; Tracer; Training; Transgenic Organisms; Viral; Visual; Visual Pathways; Visual system structure; Wild Type Mouse; Work; base; cell type; conditional mutant; experience; feature extraction; ganglion cell; genetic manipulation; in vivo; molecular marker; neuromechanism; orientation selectivity; patch clamp; receptive field; receptor; relating to nervous system; response; retinal axon; retinal imaging; visual information; visual processing

Project Summary Orientation selectivity, a fundamental feature observed throughout the early visual system, is first computed in the retina by orientation selective ganglion cells (OSGCs). Recent work has reported diverse mechanisms underlying On and Off OSGCs, yet less is known about the On-Off type. My preliminary calcium imaging data suggests that On-Off OSGCs are a major OSGC subtype in the mouse retina and they are sensitive to GABAA receptor antagonists. This proposal aims to determine the synaptic mechanisms underlying the orientation selectivity of On-Off OSGCs in the mouse retina and their central projection patterns. The lack of molecular markers for OSGCs has limited a mechanistic understand of orientation selectivity in the mammalian retina. In Aim 1, we will perform calcium imaging of RGCs to screen for On-Off OSGCs and target them for single-cell recordings. Additionally, we will use pharmacology and α-subunit specific manipulations of GABAA receptors on RGCs to determine the involvement of specific synapses in orientation selectivity. In Aim 2, we will identify the projection patterns of On-Off OSGCs to dorsal LGN using viral retrograde tracers and transgenic labeling. Learning to perform whole-cell patch-clamp recordings and retrograde tracer injections are major training goals of this grant. Results from this work will yield a mechanistic understanding of retinal orientation selectivity and provide a link between this retinal feature selectivity and higher visual processing in the thalamocortical pathway.

项目摘要 方向选择性是早期视觉系统的一个基本特征， 在视网膜中由方向选择性神经节细胞（OSGCs）计算。最近的工作报告说， 不同的机制下的开和关OSGCs，但很少知道的开-关类型。我 初步的钙成像数据表明，开-关型OSGCs是OSGCs的一种主要亚型， 小鼠视网膜，并且它们对GABAA受体拮抗剂敏感。这项建议旨在 确定突触机制的基础上的方向选择性的开关OSGCs在 小鼠视网膜及其中央投射模式。由于缺乏OSGCs的分子标记， 限制了对哺乳动物视网膜方向选择性的机械理解。目标1： 将对RGC进行钙成像，以筛选On-Off OSGCs并靶向它们进行单细胞 录音.此外，我们将使用药理学和α-亚基特异性操作GABAA RGC上的受体，以确定特定突触参与方向选择性。在 目的2，我们将利用病毒介导的免疫细胞化学技术， 逆行示踪剂和转基因标记。学习进行全细胞膜片钳记录 和逆行示踪剂注射是这项资助的主要培训目标。这项工作的结果将 产生对视网膜取向选择性的机械理解，并提供这两者之间的联系。 视网膜特征选择性和丘脑皮层通路中的高级视觉处理。