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 视网膜输出的一个主要靶点是上丘(SC)。事实上，更多类型的视网膜神经节细胞(RGC)可能 投射到SC比任何其他视网膜目标，包括外侧膝状核(LGN)。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，视网膜对SC输入的功能多样性，以及最终它是如何 对SC信号的影响，在哺乳动物中仍然知之甚少。这一差距在灵长类动物中尤为明显。 这项建议的首要目标是确定细胞类型的多样性及其传递的视觉信号 从大鼠和恒河猴的视网膜到SC。这项提议的基本原理是为了理解 在视觉引导行为中，我们必须确定视网膜信号在SC中如何汇聚和处理。 实现这一目标的第一步是确定哪种类型的RGC投射到SC，以及什么视觉信号 它们携带着。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(或分化的)，还有什么 这种专门化的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 优化病毒方法逆行感染直接投射到SC的大鼠视网膜节细胞。我们将确定 这些视网膜神经节细胞的形态多样性。我们还将确定他们的接受视野和其他视觉反应 性能，体外，使用大规模多电极阵列。结果将是一个完整的目录 大鼠脑内投射到SC的视网膜节细胞的形态和功能类型。在目标2中，我们将使用最多的 来自目标1的有效病毒方法来剖析投射到猴子SC的RGC类型的多样性。AS 在老鼠身上，我们将确定猕猴体内这些RGCs的形态多样性，并确定它们的接受性 使用大规模、高通量电生理学的视野和其他视觉响应特性。在目标3中，我们 将确定RGC对SC和LGN的投射重叠，分别用于大鼠和灵长类动物。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 投射到一个脑区而非两个脑区的视网膜节细胞的类型和功能。这个项目的总体成果 将是在大鼠和灵长类动物中投射到SC的RGC的功能和形态目录，允许 这一关键视觉回路的详细跨物种比较。这一比较很重要，因为 致力于研究啮齿动物的视觉系统，最终目的是理解人类的视觉 系统。这些数据将是设计下一阶段研究的关键，该研究将测量和操作这些功能 以确定它们在视觉加工和视觉加工中的贡献 注意力缺陷多动症和其他注意力和视觉运动障碍的行为及其潜在损害。