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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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要方向选择性是整个早期视觉系统中观察到的一个基本特征，它是第一个由定向选择性神经节细胞（OSGC）在视网膜中计算。近期工作已报道 On 和 Off OSGC 的机制多种多样，但人们对 On-Off 类型知之甚少。我的初步钙成像数据表明，开关 OSGC 是一种主要的 OSGC 亚型小鼠视网膜对 GABAA 受体拮抗剂敏感。该提案旨在确定开关 OSGC 方向选择性的突触机制小鼠视网膜及其中心投影图案。 OSGCs 分子标记的缺乏限制了对哺乳动物视网膜方向选择性的机械理解。在目标 1 中，我们将对 RGC 进行钙成像，以筛选 On-Off OSGC 并将其作为单细胞目标录音。此外，我们将使用 GABAA 的药理学和 α 亚基特异性操作 RGC 上的受体以确定特定突触参与方向选择性。在目标 2，我们将使用病毒识别 On-Off OSGC 到背侧 LGN 的投射模式逆行示踪剂和转基因标记。学习进行全细胞膜片钳记录逆行示踪剂注射是本次资助的主要培训目标。这项工作的结果将产生对视网膜方向选择性的机械理解并提供这之间的联系丘脑皮质通路中的视网膜特征选择性和更高的视觉处理能力。