Circuit formation in the visual centers

视觉中枢的回路形成

• 批准号: 9973917
• 负责人: Claude Desplan
• 金额: $ 39.63万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9973917
• 关键词: Address; Adult; Axon; Behavior; Behavior Control; Biological Models; Birth Order; Brain; Brain region; Cells; Color; Complement; Cone; Data; Dendrites; Development; Drosophila genus; Elements; Flying body movement; Funding; Ganglia; Genetic; Genomics; Grant; Individual; Interneurons; Location; Maps; Mediating; Modeling; Molecular; Molecular Genetics; Motion; Neuroglia; Neurons; Neuropil; Optic Lobe; Optics; Output; Pathway interactions; Pattern; Photoreceptors; Positioning Attribute; Process; Recording of previous events; Resources; Retina; Retinal Ganglion Cells; Rhodopsin; Rod; Role; Sensory; Signal Transduction; Speed; Testing; Vertebrates; Visual; Visual system structure; cell type; detector; experimental study; fly; insight; large datasets; mind control; nerve stem cell; neurogenesis; novel; orientation selectivity; programs; relating to nervous system; retinotopic; sensory system; single cell mRNA sequencing; single-cell RNA sequencing; tool; transcriptome; transcriptomics; visual information; visual performance; visual processing

Visual information detected by the retina is sent for further processing to deeper layers of the visual centers that feed into specialized behavior circuits. Much is known about how visual centers and local circuits function, but we do not understand how the many cell types that compose them are generated and how these circuits assemble and are coordinated between brain regions. We study the simplified, yet highly performing visual system of Drosophila for which we have obtained a deep understanding of neural diversity, mechanisms that also apply to mammalian neurogenesis. In a separately funded grant, we have generated a very large dataset where we have identified through single cell mRNA sequencing the individual transcriptome of most (169 neural types) neurons and glia in the four optic lobe ganglia, lamina, medulla, lobula and lobula plate, through six development stages starting when the neurons are first generated. This represents a huge resource that will allow us to identify the molecular pathways involved in the processes studied here. In the current proposal, we will define how the circuits formed by optic lobe neurons are assembled and how development of the different optic lobe neuropils is synchronized: Aim 1. Retinotopic projection of photoreceptors to the lamina and medulla. We will define the role of the lamina in the establishment of retinotopy in the medulla and what guides photoreceptors and lamina neurons to their retinotopic location. We will then identify the molecular guidance pathways involved in pathfinding in lamina and medulla, and determine the potential role of pioneer neurons that might guide retinotopy of the other neurons. Aim 2 Timing of differentiation and layer formation in the medulla neuropil. Medulla neurons are born from the same neural progenitors in a sequential order, a fundamental mechanism of 'temporal patterning'. We will test the model that temporal patterning allows medulla neurons to progressively innervate each layer of the lobula and of the medulla and we will define the molecular mechanisms synchronizing birth order and layer formation. Aim 3: Development of output neurons from the lobula: Visual features and optic glomeruli. Signals from the medulla are conveyed to the lobula and are then passed on to Lobula Columnar Neurons (LCNs) that connect to 'optic glomeruli' that control behavior. We will study how ~20 subtypes of LCNs connect to different layers of the lobula and to specific glomeruli in the central brain and will define the molecular mechanisms of their specific targeting. Aim 4. Building the broad-field motion pathway. Motion is computed by neurons that compare the outputs of upstream neurons in a specific orientation. We will investigate the developmental programs that instruct the dendrite orientation of the first orientation-selective neurons (T4 and T5) and how they each project to one of the 4 layers of the lobula plate that each detects motion in one of 4 cardinal directions. This study will provide fundamental insights into the coordination of various elements of a simple and amenable visual system. Our findings will not only provide novel fundamental concepts for the development of circuits for sensory processing, but will also contribute general concepts applicable to circuit formation in vertebrates.

视网膜检测到的视觉信息被发送，以进一步处理馈送视觉中心的更深层次 进入专门的行为电路。关于视觉中心和本地电路的功能知之甚少，但我们没有 了解如何生成许多组成它们的细胞类型，以及这些电路如何组装和在大脑区域之间进行协调。我们研究了果蝇的简化但高表现的视觉系统，我们对神经多样性有了深刻的了解，这也适用于哺乳动物神经发生。 在单独资助的赠款中，我们生成了一个非常大的数据集，在其中通过单细胞mRNA测序了大多数（169种神经类型）神经元和神经元的单个转录组和神经元的神经神经元，层，延迟，髓质，小叶和小叶板的六个发育阶段，该神经元首次生成了六个发育阶段。这代表了一个巨大的资源，它将使我们能够确定此处研究过程中涉及的分子途径。 在当前的建议中，我们将定义如何组装光叶神经元形成的电路，以及如何同步不同的视叶神经胶体的发展： 目标1。光感受器对薄片和髓质的视网膜投影。 我们将定义椎板在髓质中建立视网膜的作用，以及将光感受器和薄片神经元引导到其视网膜位置的原因。然后，我们将确定涉及层次和髓质途径的分子引导途径，并确定可能引导其他神经元视网膜的先锋神经元的潜在作用。 AIM 2分化和层形成的时机在延髓神经胶质中。 髓质神经元以顺序从相同的神经祖细胞出生，这是“暂时性图案”的基本机制。我们将测试暂时性模式允许延髓神经元逐渐支配小叶和髓质的每个层的模型，我们将定义分子机制同步出生顺序和层形成。 AIM 3：从小叶中开发输出神经元：视觉特征和视觉肾小球。 延髓的信号被传递到小叶，然后传递到小叶柱神经元（LCN），这些神经元（LCN） 连接到控制行为的“光学肾小球”。我们将研究约20个LCN的亚型如何连接到不同层的不同层 中央大脑中的小叶和特定的肾小球，并将定义其特定靶向的分子机制。 目标4。构建广阔的运动途径。 运动是由比较特定方向上上游神经元输出的神经元计算得出的。我们将研究指导第一个方向选择性神经元（T4和T5）的树突方向的发展程序，以及它们如何将每个叶板的四层投影到每个基本方向之一。这项研究将为简单且可正约的视觉系统的各个要素的协调提供基本的见解。我们的发现不仅将为开发感官处理的电路提供新颖的基本概念，而且还将贡献适用于脊椎动物中电路形成的一般概念。