Bridging gap in comparative biology using the tree shrew visual system

使用树鼩视觉系统弥合比较生物学的差距

• 批准号: 10480735
• 负责人: SUVA ROY
• 金额: $ 6.57万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-06-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480735
• 关键词: Animals; Area; Biological Models; Brain; Cell physiology; Cells; Color; Color Visions; Comparative Biology; Comparative Study; Cone; Electrophysiology (science); Exhibits; Eye; Gene Expression; Genes; Genetic; Genetic Screening; Genetic Variation; Incentives; Individual; Ipsilateral; Label; Light; Mammals; Measurement; Measures; Mentors; Modeling; Molecular; Molecular Genetics; Morphology; Movement; Mus; Neurophysiology - biologic function; Neurosciences; Pathology; Pattern; Peripheral; Pharmacology; Photoreceptors; Phylogenetic Analysis; Population; Primates; Process; Property; Research; Retina; Retinal Ganglion Cells; Rodent; Route; Shapes; Signal Transduction; Structure; Techniques; Testing; Tissue-Specific Gene Expression; Tracer; Transfection; Translating; Tupaiidae; Variant; Viral; Vision; Visual; Visual Cortex; Visual Pathways; Visual system structure; Work; base; cell type; color processing; density; experimental study; genetic analysis; genetic makeup; improved; insight; molecular marker; multi-electrode arrays; neural circuit; new technology; novel; optogenetics; orientation selectivity; receptive field; relating to nervous system; response; retinogeniculate; single-cell RNA sequencing; species difference; tool; transcriptomics; visual processing; visual stimulus

PROJECT SUMMARY A major dichotomy in comparative biology is the divergence of visual specializations in different species. This is prominently observed in rodents and primates - the former specialized to detect movement in low light conditions while the latter specialized to detect fine spatial patterns and color. A large body of research on these visual systems points to fundamental differences in structural, functional and genetic makeup of neural circuits in the early visual pathway. This makes it difficult to understand how different features of the visual world are selectively processed in the retina and in the brain. Achieving a comprehensive understanding of higher visual processing requires an understanding of visual processing in not just rodents and primates but also in other species. This also calls for the use of novel technologies for probing and translating findings across different visual systems. Tree shrew is a small animal at the phylogenetic midpoint of rodents and primates, with highly developed retina and visual cortex. Because of their diurnal and excellent color vision, tree shrews have been extensively used as a model system for understanding color processing in the mammalian visual system. This proposal will combine advanced techniques such as large-scale measurements of neural population activity, genetic screening and viral tracing to achieve detailed functional characterization of retinal ganglion cells and their connectivity to the LGN. In aim 1, we will use a high-density multi-electrode array for recording activity of large populations of retinal ganglion cells (RGCs), to reveal how morphologically and functionally distinct RGC types encode distinct visual features in their responses. To determine the diversity of gene expression in functionally distinct RGCs, in aim 2, we will employ high- throughput single-cell RNA sequencing of RGCs. We will also test for the presence of well-established molecular markers for RGC types, in the tree shrew retina. Finally, in aim 3, we will use viral labeling to determine the precise pattern of convergence from the retina to the LGN. By measuring the response of optogenetically stimulated RGCs, we will establish the lamina specific LGN projections of functionally distinct RGC types. These experiments will provide a comprehensive understanding of the structure and function of neural circuits in the early visual pathway, that produce distinct visual specializations in different species. This study will establish tree shrew as a model system for comparative studies on visual processing in higher mammals and provide novel insights into the pathologies of vision.

项目摘要 比较生物学中的一个主要二分法是不同物种视觉特化的差异。 这在啮齿动物和灵长类动物中很明显--前者专门在弱光下探测运动 后者专门用于检测精细的空间图案和颜色。大量的研究表明 这些视觉系统指出了神经系统在结构、功能和遗传组成上的根本差异。 早期视觉通路中的回路这使得人们很难理解视觉的不同特征 在视网膜和大脑中有选择地处理世界。全面了解 高级视觉处理不仅需要了解啮齿动物和灵长类动物的视觉处理， 也在其他物种中。这也需要使用新技术来探索和翻译研究结果 不同的视觉系统。树鼩是一种小型动物，处于啮齿动物系统发育的中点， 灵长类动物，具有高度发达的视网膜和视觉皮层。因为它们白天活动和出色的色觉， 树鼩已经被广泛地用作理解人类的颜色处理的模型系统。 哺乳动物视觉系统该提案将联合收割机与先进技术相结合， 神经群体活性的测量、遗传筛选和病毒追踪，以实现详细的功能 视网膜神经节细胞的表征及其与LGN的连接性。在aim 1中，我们将使用高密度 多电极阵列用于记录大量视网膜神经节细胞（RGC）的活动，以揭示 形态和功能不同的RGC类型在其反应中编码不同的视觉特征。到 为了确定功能不同的RGC中基因表达的多样性，在目标2中，我们将采用高水平的 RGC的单细胞RNA测序。我们还将测试是否存在 RGC类型的分子标记，在树鼩视网膜。最后，在目标3中，我们将使用病毒标记， 确定从视网膜到LGN的精确会聚模式。通过测量 通过光遗传学刺激RGCs，我们将建立功能不同的LGN投射的层特异性LGN投射。 研资局类型。这些实验将提供一个全面的了解的结构和功能， 早期视觉通路中的神经回路，在不同物种中产生不同的视觉特化。这 这项研究将建立树鼩作为比较研究高等动物视觉加工的模型系统。 哺乳动物，并提供新的见解的病理视觉。