Automated analyses of behavior in response to visual stimuli

自动分析响应视觉刺激的行为

• 批准号: 9350341
• 负责人: ROBBERT J CRETON
• 金额: $ 35.45万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9350341
• 关键词: Address; Affect; Algorithms; Animal Model; Behavior; Behavioral; Behavioral Assay; Biological Assay; Biological Models; Blindness; Chorion; Cluster Analysis; Color Visions; Complex; Custom; DNA Sequence Alteration; Defect; Development; Embryo; Environmental Risk Factor; Eye; Eye diseases; Fertilization; Genetic; Goals; Human; Image; Laboratories; Larva; Measures; Methodology; Molecular; Monitor; National Eye Institute; Natural regeneration; Neurons; Ocular Physiology; Outcome; Photoreceptors; Physical shape; Prevention; Process; Quality of life; Recovery; Recovery of Function; Structure of retinal pigment epithelium; System; Testing; United States National Institutes of Health; Vision; Visual; Visual impairment; Visual system structure; Visually Impaired Persons; Work; Zebrafish; base; behavior influence; behavioral response; computer generated; disability; field study; genetic manipulation; high resolution imaging; high throughput analysis; imaging system; improved; in vivo; interest; lens; neural patterning; novel; optic stalk; productivity loss; public health relevance; regenerative; relating to nervous system; response; small molecule; small molecule libraries; success; tool; visual stimulus

 DESCRIPTION (provided by applicant): Visual impairments affect 285 million people worldwide: 39 million people are blind and 246 million people have low vision. Novel treatments are urgently needed and several lines of evidence suggest that it may be possible to restore vision by regenerating photoreceptors and neural connections. The interest in such regenerative processes is highlighted by the audacious goal of the National Eye Institute at the NIH to `regenerate neurons and neural connections in the eye and visual system'. However, as novel methodologies are developed, a critical question will need to be addressed: how do we monitor in vivo for functional success? An effective approach to monitor for functional success in animal model systems is the analysis of behavior, since behavioral analyses can reveal subtle functional defects, even if the visual system appears normal by morphological criteria. The current project is focused on the automated analysis of behavior in response to visual stimuli, using zebrafish larvae as a model system. Zebrafish larvae are ideally suited for such studies, since high-throughput analyses of behavior can be combined with genetics, high-resolution imaging and experimental manipulations. The long-term goal of the project is to contribute to the prevention and treatment of visual defects, through an in-depth understanding of behavior in response to visual stimuli. The project is guided by the overall hypothesis that the automated analysis of zebrafish behavior is an effective and sensitive approach to identify specific visual defects and monitor the recovery from such defects. This hypothesis will be tested in three specific aims. The first aim is to further improve the automated analysis of zebrafish larval behavior in response to visual stimuli, using a custom-built imaging system. Novel algorithms and assays will be developed and the behavioral responses to visual stimuli will be examined at different developmental stages. The second aim is to identify changes in behavioral profiles caused by specific defects in the visual system. We will analyze behavior in larvae with genetic mutations that affect development of the optic stalk, photoreceptors, retinal pigment epithelium, hyaloid vasculature and the lens. The third aim is to identify behavioral profiles which indicate a recovery from visual defects. Zebrafish have a remarkable capacity for regeneration of the visual system and the behavioral responses to visual stimuli constitute an in vivo monitor for the recovery of visual function. The project will also examine if functional recoveries can be stimulated by small molecules, which have been successful in stimulating regeneration in other systems. The expected outcome from this work includes a better basic understanding of behaviors that are influenced by visual stimuli and high-throughput tools to evaluate treatments of blindness and low vision. The developed tools may be used in future research to screen for a broad range of genetic and environmental factors that cause visual defects and to screen small molecule libraries for novel treatments of blindness and low vision.

 描述（应用程序提供）：视觉障碍影响全球2.85亿人：3900万人盲目，2.46亿人的视力低下。迫切需要新的治疗方法，几条证据表明，可以通过再生感受器和神经连接来恢复视力。 NIH国家眼科研究所的大胆目标强调了对这种再生过程的兴趣，即“眼睛和视觉系统中的神经元和神经元连接”。但是，随着新方法的开发，将需要解决一个关键问题：我们如何监视体内功能成功？监测动物模型系统功能成功的有效方法是对行为的分析，因为行为分析可以揭示出细微的功能缺陷，即使视觉系统通过形态标准正常。当前的项目以斑马鱼幼虫为模型系统的响应于视觉刺激的行为分析。斑马鱼幼虫非常适合此类研究，因为对行为的高通量分析可以与遗传学，高分辨率成像和实验操作结合使用。该项目的长期目标是通过对视觉刺激的响应对行为的深入了解，为视觉缺陷的预防和治疗做出贡献。该项目的指导是总体假设，即斑马鱼行为的自动分析是一种有效而敏感的方法，可以识别特定的视觉缺陷并监视从此类缺陷中恢复的方法。该假设将以三个特定目的进行检验。第一个目的是使用定制的成像系统进一步改善斑马鱼幼虫行为的自动分析。将开发新的算法和测定，并将在不同的发育阶段检查对视觉刺激的行为反应。第二个目的是确定视觉系统中特定缺陷引起的行为概况的变化。我们将通过影响视茎，感光体，视网膜色素上皮，透明脉管系统和镜头的遗传突变分析幼虫的行为。第三个目的是确定表明一个表明的行为概况 从视觉缺陷中恢复。斑马鱼具有显着的视觉系统再生能力，对视觉刺激的行为响应构成了视觉功能恢复的体内监视器。该项目还将检查小分子是否可以刺激功能恢复，这些分子在刺激其他系统的再生方面成功。这项工作的预期结果包括对受视觉刺激和高通量工具影响的行为的更好的基本理解，以评估失明和低视力的治疗方法。开发的工具可以在未来的研究中使用，以筛选出引起视觉缺陷的广泛遗传和环境因素，并筛选小分子库，以供新颖的盲目治疗和低视力治疗。