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.

项目摘要 视网膜输出的主要目标是上级丘（SC）。事实上，更多的视网膜神经节细胞（RGC）类型可能 投射到SC的比包括外侧膝状体核（LGN）的任何其它视网膜靶更高。理解 视网膜对SC的输入是重要的，因为SC在一系列注意力和决策中起着重要作用 啮齿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， 美国国立卫生研究院然而，视网膜输入SC的功能多样性，以及最终它是如何 影响SC信号传导，在哺乳动物中仍然知之甚少。这种差距在灵长类动物中尤为明显。 这项提案的首要目标是确定细胞类型的多样性和它们传递的视觉信号 在大鼠和恒河猴中从视网膜到SC。提出这一建议的理由是，要了解 在视觉引导行为中，我们必须确定视网膜信号如何在SC中会聚和处理。 要达致这个目标，第一步是确定研资局的哪类项目会投射到SC，以及有什么视觉信号 他们携带。在啮齿动物和猕猴身上进行这些实验不仅对理解 从啮齿动物到灵长类动物的大脑中，哪些特定的视觉通路是保守的（或发散的）， 这种专门化赋予每个物种的进化优势。在本建议的目标1中，我们将使用和 优化逆转感染直接投射到大鼠SC的RGCs的病毒方法。康贝特人将以 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 性能，离体，使用大规模的多电极阵列。结果将是一个完整的目录， 在大鼠脑中投射到SC的RGCs的形态和功能类型。在目标2中，我们将使用 目的1中的有效病毒方法，以剖析投射到猴SC的RGC类型的多样性。作为 用大鼠，我们将确定猕猴这些RGCs的形态多样性，并确定它们的感受性。 场和其他视觉响应特性，使用大规模，高通量电生理学。在目标3中，我们 将分别确定大鼠和灵长类动物的RGC投射到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。该项目的总体成果 将是RGC的功能和形态目录，在大鼠和灵长类动物中投射到SC， 对这个关键视觉回路进行详细的跨物种比较。这种比较很重要，因为 研究致力于啮齿动物的视觉系统，最终目的是了解人类的视觉 系统这些数据将是设计下一阶段研究的关键，这些研究将测量和操纵这些功能。 的特定群体的SC投射RGC，以确定其对视觉处理的贡献， 注意力缺陷多动障碍和其他注意力和视觉障碍的行为及其潜在损害。