Receptive field coordination across mosaics of diverse retinal ganglion cell types in the mammalian retina

哺乳动物视网膜中不同视网膜神经节细胞类型镶嵌体的感受野协调

• 批准号: 10376332
• 负责人: Gregory Darin Field
• 金额: $ 34.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376332
• 关键词: Animals; Axon; Brain; Cells; Code; Data; Data Analyses; Dendrites; Development; Developmental Process; Ensure; Event; Exhibits; Eye; Genetic; Goals; Immunohistochemistry; Lead; Learning; Location; Measurement; Measures; Methods; Mosaicism; Motion; Nature; Neurons; Noise; Outcome; Outcomes Research; Pharmacology; Physiological; Population; Positioning Attribute; Process; Property; Rattus; Research; Retina; Retinal Ganglion Cells; Role; Sampling; Sensory; Shapes; Signal Transduction; Specificity; Structure; Synapses; Testing; TimeLine; Transgenic Mice; Vision; Visual; Visual Fields; Work; body position; cell type; dark rearing; experience; experimental study; ganglion cell; innovation; neural circuit; novel; programs; receptive field; response; sight restoration; theories; visual processing

Throughout the brain, neural circuits are composed of diverse cell types. In the retina, cell types are spatially organized into mosaics, in which the receptive fields of each type approximately tile space. This organization ensures that the computations performed by each cell type occur uniformly across the visual field, with no gaps or gluts in processing. This exquisite coordination within each cell type to uniformly cover space raises the question, ‘is there coordination across cell types?’ In general, this coordination could manifest as either a tendency toward alignment, or anti-alignment, between two mosaics of receptive fields. Our central hypothesis is that mosaics of receptive fields are intricately coordinated across retinal cell types and that this coordination reflects fundamental organizing principles for how the retina processes natural scenes. We demonstrate with preliminary data that across four retinal ganglion cell (RGC) types in the rat retina, mosaics of receptive fields are intricately coordinated. Specifically, mosaics of ON and OFF RGC types that signal similar visual features are consistently anti-aligned. Meanwhile, mosaics of OFF and OFF types that signal distinct features are also anti-aligned while mosaics of ON and ON types are aligned. Finally, we show that across ON and OFF types that signal distinct visual features the mosaics are statistically independent in their spatial arrangement. The objectives of this proposal are to build upon these observations to (1) understand the mechanisms that underlie inter-mosaic coordination (Aim 1), (2) determine how and when this coordination develops (Aim 2), and (3) to determine the significance of inter-mosaic coordination of visual as well as how extensively mosaics are coordinated across additional RGC types (Aim 3). This proposed research is significant because it will uncover an entirely new phenomenon in the vertebrate retina: inter-mosaic coordination across diverse cell types with diverse receptive field properties. It will also reveal either new developmental mechanisms, or new roles for previously established mechanisms in coordinating mosaics across RGC types. It will also make novel predictions for how downstream neurons could pool over retinal inputs to produce orientation and direction tuned responses. Finally, this work is significant because it extends the theoretical basis (e.g. ‘efficient coding theory’) of how we understand the organization of retinal processing. The proposed research is innovative because it applies a recently developed analytical framework to large-scale population measurements of RGC receptive fields with the goal of understanding the contributions of cell position and synaptic specificity to inter-mosaic coordination. Furthermore, the work is conceptually innovative because it shows receptive field mosaics are coordinated and identifies the benefits of coordination to vision. The expected outcome of this research is a novel set of mechanisms and developmental process that yield functional coordination across distinct cell types in the retina. We anticipate these discoveries as being fundamental and impactful to understanding the retina and sensory processing

在整个大脑中，神经回路由潜水细胞类型组成。在视网膜中，细胞类型在空间上是 组织成镶嵌物，其中每种类型的接收场大约是瓷砖空间。这个组织 确保每种单元类型执行的计算在整个视野上均匀地出现，没有间隙 或加工中的gluts。每种单元格内的这种独家协调都统一覆盖了空间，这提出了一个问题：“跨单元类型是否协调？”，这种协调可以表现为一种趋势 在两个接受田的镶嵌物之间进行对准或反对准。我们的中心假设是 在视网膜细胞类型中，接收场的镶嵌物复杂地协调，这种协调反映了 视网膜如何处理自然场景的基本组织原理。我们用初步演示 大鼠视网膜中四种视网膜神经节细胞（RGC）类型的数据，接收场的镶嵌物很复杂 协调性。特别是，发出类似视觉特征的ON和OFF RGC类型的镶嵌物是一贯的 反将。同时，隔离和关闭类型的镶嵌物也可以抗结，而 ON和ON类型的镶嵌物是对齐的。最后，我们证明了在开关类型中，可以发出不同的信号 视觉特征在其空间排列中，镶嵌物在统计上是独立的。该提议的目标是基于这些观察结果，以（1）了解基于摩萨群岛间协调的机制（目标1），（2）确定这种协调发展的方式以及何时（目标2）以及（3）确定摩西质间协调的显着性，以确定可视化的摩托学间协调以及如何互相互为互相互动（目标）。研究之所以重要，是因为它将在脊椎动物视网膜中揭示一个全新的现象：跨潜水员细胞类型的摩西间协调 特性。它还将揭示新的发展机制或以前建立的新角色 RGC类型的协调镶嵌机制。它还将为下游做出新颖的预测 神经元可以在残留输入上汇集以产生方向和方向调节响应。最后，这项工作是 意义重大，因为它扩展了我们如何理解视网膜处理组织的理论基础（例如“有效的编码理论”）。拟议的研究具有创新性，因为它应用了最近开发的 RGC接受场的大规模种群测量的分析框架，目的是了解细胞位置和突触特异性对摩西间协调的贡献。此外， 工作在概念上是创新的，因为它表明接受田间马赛克是协调的，并确定了与视觉协调的好处。这项研究的预期结果是一组新型的机制和发育过程，可在视网膜中不同细胞类型上产生功能协调。我们期待这些 发现对理解视网膜和感官处理是根本和影响的