Visual Signal Transformation in the Retinocollicular Pathway

视网膜小球通路中的视觉信号转换

• 批准号: 9187019
• 负责人: Jianhua Cang
• 金额: $ 47.44万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9187019
• 关键词: Address; Affect; Anatomy; Behavior; Brain; Calcium; Cells; Data; Disease; Dyslexia; Employee Strikes; Foundations; Genetic; Goals; Grant; Image; Individual; Inherited; Injection of therapeutic agent; Interneurons; Knock-in Mouse; Label; Location; Maps; Mental disorders; Methodology; Midbrain structure; Modeling; Motion; Movement; Mus; Nervous system structure; Neurons; Pathway interactions; Physiological; Population; Presynaptic Terminals; Process; Property; Research; Research Personnel; Retina; Retinal; Retinal Ganglion Cells; Sampling; Schizophrenia; Signal Transduction; Structure; Synapses; System; Testing; Time; Transgenic Mice; Viral; Vision; Vision research; Visual; Visual system structure; Whole-Cell Recordings; autism spectrum disorder; brain circuitry; calcium indicator; cell type; excitatory neuron; experimental study; imaging modality; in vivo; inhibitory neuron; insight; multimodality; nervous system disorder; optogenetics; public health relevance; relating to nervous system; response; retinal axon; retinotopic; signal processing; superior colliculus Corpora quadrigemina; tool; two-photon; visual information; visual processing; visual stimulus

 DESCRIPTION (provided by applicant): How visual information is processed and transformed in the nervous system is a fundamental question in vision research. Given its clear importance in visually-guided behaviors and the available genetic tools, the mouse superior colliculus (SC) holds great promise for understanding visual signal transformation and its mechanisms. The SC is a layered structure important for multimodal integration and sensorimotor transformation, and its superficial layers are purely visual and receive direct retinotopic inputs from the retina. In his proposal, the investigators will study the brain circuitry and synaptic mechanisms underlying the important transformations that take place in the retinocollicular pathway, especially the processing of motion direction. First, 2-photon calcium imaging will be performed to determine the direction selectivity of individual SC neurons and their spatial organization. These experiments will establish whether there is a depth-, region-, and/or cell type-specific organization of direction selectivity in the superficial SC, thereby forming a foundation for the following aims. Second, the investigators will determine the response properties of the retinal input that project to the SC. Genetically-encoded calcium indicators will be expressed in retinal ganglion cells and 2- photon imaging will be performed to visualize their axonal terminals in the colliculus. Third, the methods of imaging retinal terminals and collicular neurons will be used in a line of transgenic mice where retinocollicular projections are spatially altered, in order to determine whether direction selective retinal input is required for the direction selectivity in th SC. Finally, the investigator will perform in vivo whole cell recording to study visually-evoked responses in the SC. These experiments will be performed in transgenic mice where excitatory SC neurons can be silenced by optogenetic stimulation, thereby exposing the retinal input to the recorded cells. By comparing the selectivity of the total and retinal input to individual SC neurons, these experiments will start to reveal the synaptic mechanisms underlying the processing and transformation of direction selectivity in the retinocollicular pathway. Together, these experiments will generate important data needed for a complete understanding of visual processing in the brain. Because normal visual processing is compromised in a number of neurological and psychiatric disorders, such as dyslexia, schizophrenia and autism spectrum disorders, these studies will provide insights for the understanding and treatment of these disorders.

 描述（由应用程序提供）：在神经系统中如何处理和转换视觉信息是视力研究中的一个基本问题。鉴于其在视觉引导的行为和可用的遗传工具中的重要性，小鼠超级胶囊（SC）具有理解视觉信号转换及其机制的巨大希望。 SC是一种对多模式整合和感觉运动转换重要的分层结构，其表层层纯粹是视觉效果，并从视网膜中接收直接的视网膜输入。在他的提案中，研究人员将研究在视网膜途径中发生的重要变换的脑电路和突触机制，尤其是运动方向的处理。首先，将执行2光子钙成像，以确定单个SC神经元及其空间组织的方向选择性。这些实验将确定是否存在浅表SC中方向选择性的深度，区域和/或细胞类型的组织，从而为以下目的构成基础。其次，研究人员将确定该项目对SC的剩余输入的响应属性。遗传编码的钙指示剂将在视网膜神经节细胞中表达，并将执行2-光子成像以可视化胶囊中的轴突末端。第三，对残留末端和丘神经元进行成像的方法将用于转基因小鼠的线，在该系列中，空间改变了视网膜细胞项目，以确定SC中的方向选择性是否需要方向选择性残留输入。最后，研究者将在体内进行全细胞记录，以研究SC中的视觉诱发响应。这些实验将在转基因小鼠中进行，在这些小鼠中可以通过光遗传学刺激沉默，从而通过比较单个SC神经元的总和和残留输入的选择性来暴露这些实验，这些实验将开始揭示突触机制的潜在机制，从而揭示了在vetinocollicaltolular pathway的方向选择性的依据。总之，这些实验将产生对大脑视觉处理的完整了解所需的重要数据。由于正常的视觉处理在许多神经系统和精神疾病中受到损害，例如阅读障碍，精神分裂症和自闭症谱系障碍，因此这些研究将为理解和治疗这些疾病提供见解。