Visual signaling from retina to superior colliculus

从视网膜到上丘的视觉信号

• 批准号: 10608278
• 负责人: Gregory Darin Field
• 金额: $ 52.41万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608278
• 关键词: Accounting; Animal Model; Area; Attention; Attention deficit hyperactivity disorder; Axon; Behavior; Behavioral; Biological Models; Biomedical Research; Blindness; Brain; Catalogs; Cell Communication; Cells; Classification; Classification Scheme; Data; Decision Making; Dedications; Disease; Dorsal; Electrophysiology (science); Endowment; Future; Genes; Genetic; Genetic Techniques; Glaucoma; Goals; Human; Impairment; Infection; Injections; Knowledge; Label; Lateral Geniculate Body; Learning; Light; Logic; Macaca; Macaca mulatta; Mammals; Measures; Methods; Modeling; Monkeys; Morphology; Mus; Neurosciences; Outcome; Output; Pathway interactions; Pattern; Physiology; Play; Population; Primates; Process; Property; Proteins; Rattus; Recombinant adeno-associated virus (rAAV); Reporter; Research; Research Support; Retina; Retinal Diseases; Retinal Ganglion Cells; Retinitis Pigmentosa; Rodent; Role; Shapes; Signal Transduction; Techniques; Testing; Transgenic Animals; Translating; United States National Institutes of Health; Viral; Virus; Vision; Visual; Visual Pathways; Visual System; Work; autism spectrum disorder; awake; cell type; density; design; experimental study; fascinate; in vivo evaluation; insight; multi-electrode arrays; nonhuman primate; novel; novel strategies; optic nerve disorder; optogenetics; orientation selectivity; promoter; receptive field; response; retinogeniculate; retinotectal; signal processing; superior colliculus Corpora quadrigemina; transmission process; visual motor; visual processing

Project Summary A major target of retinal output is the superior colliculus (SC). In fact, more retinal ganglion cell (RGC) types may project to the SC than any other retinal target including the lateral geniculate nucleus (LGN). Understanding retinal input to SC is important because SC plays a major role in a range of attentional and decision-making processes in both rodents and primates – two major model systems used in biomedical research supported by the National Institutes of Health. However, the functional diversity of retinal input to SC, and ultimately how it impacts SC signaling, remains poorly understood in mammals. This gap is particularly pronounced in primates. The overarching goal of this proposal is to determine the diversity of cell types and the visual signals they transmit from the retina to SC in rats and rhesus monkeys. The rationale for this proposal is that to understand the role of SC in visually guided behaviors, we must determine how retinal signals converge and are processed in SC. The first step toward achieving this goal is to determine which RGC types project to SC and what visual signals they carry. Performing these experiments in both rodents and macaques is critical not just for understanding which specific visual pathways are conserved (or diverge) from rodent to the primate brain, but also what evolutionary advantages such specializations endow to each species. In Aim 1 of this proposal, we will use and optimize viral methods for retrogradely infecting RGCs that project directly to SC in rats. We will determine the morphological diversity of these RGCs. We will also determine their receptive fields and other visual response properties, ex vivo, using large-scale multi-electrode arrays. The outcome will be a complete catalog of the morphological and functional types of RGCs that project to SC in the rat brain. In Aim 2, we will use the most effective viral approaches from Aim 1 to dissect the diversity of RGC types that project to SC in monkeys. As with rats, we will determine the morphological diversity of these RGCs in macaques and determine their receptive fields and other visual response properties using large-scale, high throughput electrophysiology. In Aim 3, we will determine the overlap of RGC projections to SC and LGN, separately for rats and primates. Retrograde viruses injected into SC and LGN will carry genes for different fluorescent proteins that will allow us to determine the types and functions of RGCs that project to one versus both brain areas. The overall outcome of this project will be a functional and morphological catalog of RGCs that project to SC in rats and primates, allowing for detailed cross-species comparison of this key visual circuit. This comparison is important given how much research is dedicated to the rodent visual system with the ultimate aim of understanding the human visual system. The data will be critical for designing next-stage studies that will measure and manipulate the functions of specific populations of SC-projecting RGCs in order to determine their contributions to visual processing and behavior and their potential impairments in ADHD and other attentional and visuomotor disorders.

项目概要 视网膜输出的主要目标是上丘（SC）。事实上，更多的视网膜神经节细胞（RGC）类型可能 与包括外侧膝状核 (LGN) 在内的任何其他视网膜目标相比，投射到 SC 的能力更强。理解 视网膜对 SC 的输入很重要，因为 SC 在一系列注意力和决策中发挥着重要作用 啮齿类动物和灵长类动物的过程——生物医学研究中使用的两个主要模型系统，由 美国国立卫生研究院。然而，视网膜输入 SC 的功能多样性，以及最终如何实现 影响 SC 信号传导，但在哺乳动物中仍知之甚少。这种差距在灵长类动物中尤其明显。 该提案的总体目标是确定细胞类型的多样性及其传输的视觉信号 在大鼠和恒河猴中，从视网膜到 SC。该提案的基本原理是为了了解角色 为了了解 SC 在视觉引导行为中的作用，我们必须确定视网膜信号如何在 SC 中汇聚和处理。 实现这一目标的第一步是确定哪些 RGC 类型投射到 SC，以及哪些视觉信号 他们携带。在啮齿动物和猕猴身上进行这些实验不仅对于理解至关重要 哪些特定的视觉通路从啮齿动物到灵长类动物的大脑是保守的（或分歧的），还有哪些 这种专业化赋予每个物种进化优势。在本提案的目标 1 中，我们将使用和 优化逆行感染直接投射到大鼠 SC 的 RGC 的病毒方法。我们将确定 这些 RGC 的形态多样性。我们还将确定他们的感受野和其他视觉反应 使用大规模多电极阵列进行离体特性。结果将是一个完整的目录 大鼠大脑中投射到 SC 的 RGC 的形态和功能类型。在目标 2 中，我们将使用最多的 目标 1 中的有效病毒方法可以剖析猴子中投射到 SC 的 RGC 类型的多样性。作为 与大鼠一起，我们将确定猕猴中这些 RGC 的形态多样性并确定它们的接受性 使用大规模、高通量电生理学来研究视场和其他视觉反应特性。在目标 3 中，我们 将分别确定大鼠和灵长类动物的 RGC 投影到 SC 和 LGN 的重叠。逆行 注入 SC 和 LGN 的病毒将携带不同荧光蛋白的基因，这将使我们能够确定 投射到一个或两个大脑区域的 RGC 的类型和功能。本项目的总体成果 将是 RGC 的功能和形态学目录，可投射到大鼠和灵长类动物的 SC，从而允许 该关键视觉回路的详细跨物种比较。这种比较很重要，因为有多少 研究致力于啮齿动物视觉系统，最终目的是了解人类视觉 系统。这些数据对于设计测量和操纵函数的下一阶段研究至关重要 SC 投射 RGC 的特定群体，以确定它们对视觉处理和 行为及其对多动症和其他注意力和视觉运动障碍的潜在损害。