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 残留输出的主要目标是上丘（SC）。实际上，更多的残留神经节细胞（RGC）类型可能 投影到SC的项目比任何其他视网膜靶标（包括侧向基因核（LGN））。理解 SC的视网膜输入很重要，因为SC在一系列注意力和决策中起着重要作用 啮齿动物和主要的过程 - 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。但是，剩余输入到SC的功能多样性，最终如何 影响SC信号传导，在哺乳动物中仍然了解得很糟糕。这个差距在私人中特别明显。 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 从视网膜到大鼠和恒河猴的SC。该提议的理由是了解角色 在视觉引导行为中的SC，我们必须确定视网膜信号如何融合并在SC中进行处理。 实现此目标的第一步是确定要进行哪种RGC类型项目以及哪些视觉信号 他们携带。在啮齿动物和猕猴中进行这些实验不仅对理解至关重要 哪种特定的视觉途径是从啮齿动物到素数的保守（或分歧），但也是什么 进化优势赋予了每个物种。在本提案的目标1中，我们将使用和 优化直接投射到大鼠SC的逆行感染的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接受场和其他视觉响应 属性，ex vivo，使用大型多电极阵列。结果将是完整的目录 将RGC的形态和功能类型投射到大鼠大脑中。在AIM 2中，我们将使用最多 AIM 1的有效病毒方法是为了剖析投影到猴子SC的RGC类型的多样性。作为 使用大鼠，我们将在猕猴中确定这些RGC的形态多样性，并确定它们的接受性 使用大规模的高吞吐量电生理学的场和其他视觉响应特性。在AIM 3中，我们 将确定RGC项目与SC和LGN的重叠，分别为老鼠和私人。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 将RGC与两个大脑区域相比的RGC的类型和功能。该项目的总体结果 将是将RGC的功能性和形态目录，该目录将在大鼠和初级中进行SC，从而允许 此关键视觉电路的详细跨物种比较。考虑到多少，这种比较很重要 研究专门用于啮齿动物的视觉系统，其最终目的是了解人类的视觉 系统。数据对于设计将测量和操纵功能的下一阶段研究至关重要 为了确定其对视觉处理的贡献和 行为及其在多动症以及其他注意力和视觉运动障碍中的潜在障碍。