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，神经回路由不同的细胞类型组成。在视网膜中，细胞类型在空间上是 组织成马赛克，其中每种类型的感受野大约是平铺空间。这个组织 确保每种细胞类型执行的计算在视野中均匀发生，没有间隙 或加工过剩。每种细胞类型内这种均匀覆盖空间的精致协调提出了一个问题：“跨细胞类型是否存在协调？”一般来说，这种协调可能表现为一种趋势 两个感受野马赛克之间的对齐或反对齐。我们的中心假设是 感受野的马赛克在视网膜细胞类型之间错综复杂地协调，这种协调反映了 视网膜如何处理自然场景的基本组织原则。我们初步论证 数据表明，在大鼠视网膜的四种视网膜神经节细胞（RGC）类型中，感受野的马赛克是错综复杂的 协调。具体来说，表示相似视觉特征的 ON 和 OFF RGC 类型的马赛克是一致的 反对齐。同时，表示不同特征的 OFF 和 OFF 类型的马赛克也是反对齐的，而 ON 和 ON 类型的马赛克对齐。最后，我们表明，在 ON 和 OFF 类型中，信号不同 视觉特征 马赛克的空间排列在统计上是独立的。该提案的目标是在这些观察的基础上（1）了解马赛克间协调的机制（目标 1），（2）确定这种协调如何以及何时发展（目标 2），以及（3）确定视觉马赛克间协调的重要性以及如何广泛地协调马赛克在其他 RGC 类型中的协调（目标 3）。这项拟议的研究意义重大，因为它将揭示脊椎动物视网膜中的一个全新现象：具有不同感受野的不同细胞类型之间的镶嵌间协调 特性。它还将揭示新的发展机制，或先前建立的新角色 协调跨 RGC 类型的嵌合体的机制。它还将对下游如何进行新颖的预测 神经元可以汇集视网膜输入以产生方向和方向调整的反应。最后，这部作品是 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 感受野大规模群体测量的分析框架，目的是了解细胞位置和突触特异性对镶嵌间协调的贡献。此外， 这项工作在概念上是创新的，因为它表明感受野马赛克是协调的，并确定了协调对视觉的好处。这项研究的预期结果是一套新颖的机制和发育过程，可以在视网膜中的不同细胞类型之间产生功能协调。我们预计这些 这些发现对理解视网膜和感觉处理具有基础性和影响力