Assessment of the development of auditory function

听觉功能发育评估

• 批准号: 7738603
• 负责人: ZHONGMIN LU
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738603
• 关键词: Acoustics; Adult; Audiometry; Auditory; Auditory Evoked Potentials; Auditory Threshold; Behavioral; Biological Models; Communities; Defect; Development; Disease; Embryo; Embryology; Equilibrium; Evolution; Fertilization; Fishes; Frequencies; Gene Targeting; Genes; Genetic; Goals; Hair Cells; Hearing; Hearing Tests; Hearing problem; Human; Imagery; Knowledge; Labyrinth; Larva; Measures; Methods; Modeling; Organism; Research; Sensory Hair; Staging; Stimulus; Time; TimeLine; Vertebrates; Zebrafish; age group; classical conditioning; critical period; deafness; genetic manipulation; hatching; human disease; in vivo; insight; mutant; novel; positional cloning

DESCRIPTION (provided by applicant): The zebrafish (Danio rerio) has become a unique vertebrate model for human disease research in hearing and balance because of a combination of powerful genetics, excellent embryology, and exceptional in vivo visualization in one organism. Recent studies use forward and reverse genetic manipulations and developmental approaches to generate a large variety of zebrafish hearing mutants in order to identify novel deafness genes and investigate auditory functions of target genes. However, auditory abilities of larval zebrafish are unknown due to lack of a method that can evaluate hearing function of zebrafish at early stages. This project has two specific aims. First, the PI will develop a reliable method that is suitable for determining auditory abilities of zebrafish larvae. There are two general ways (loudspeaker and shaker table) to produce acoustic stimuli that can activate sensory hair cells in the inner ear of fish. There are two common methods (auditory evoked potential recording and behavioral classical conditioning) to assess the auditory function of fish. The PI will investigate what setup and method are best suitable for determining auditory thresholds of young larval zebrafish. Results of this project will provide the zebrafish research community a hearing test that can precisely assess hearing defects of zebrafish mutants used for studying auditory disorders in humans. Second, the PI will investigate how the auditory function of wild-type zebrafish enhances during the early development after fertilization. The timeline of development of best frequency, best sensitivity, and audible frequency range will be determined for zebrafish of several different age groups from just hatching to adulthood. The PI will determine the critical period of development of hearing function and identify the time when the auditory capacities reach a plateau. We know little about what young larval zebrafish can hear and how their auditory function develops. Results from this study will fill this knowledge gap to further establish the zebrafish as a model system for auditory research. Easy accessibility of zebrafish embryos right after fertilization makes zebrafish an ideal candidate to investigate the early hearing development in vertebrates. Results from this study will help us better understand evolution of the early development of auditory function in vertebrates including humans. The method developed by this project will enable the zebrafish research community to precisely assess auditory functional defects of zebrafish mutants used for studying human hearing disorders and help further establish the zebrafish as a vertebrate model system for human hearing research. Results from this study will fill the knowledge gap of auditory abilities of larval zebrafish and provide insight into evolution of the early development of auditory function in vertebrates including humans.

描述（由申请人提供）：斑马鱼（Danio rerio）已成为一种独特的脊椎动物模型，用于在一种生物体中结合强大的遗传学，出色的胚胎学和异常的体内可视化，从而在听力和平衡方面进行人类疾病研究。最近的研究使用前向和反向遗传操作和发育方法来产生各种各样的斑马鱼听力突变体，以识别新型的聋哑基因并研究靶基因的听觉功能。但是，由于缺乏可以评估斑马鱼在早期阶段的听力功能的方法，幼虫的听觉能力尚不清楚。该项目有两个具体的目标。首先，PI将开发一种可靠的方法，适合确定斑马鱼幼虫的听觉能力。有两种一般的方法（扬声器和振动台）产生声学刺激，可以激活鱼内耳的感觉毛细胞。有两种常见方法（听觉诱发潜在记录和行为经典条件）来评估鱼类的听觉功能。 PI将研究哪种设置和方法最适合确定年轻幼虫斑马鱼的听觉阈值。该项目的结果将为斑马鱼研究社区提供一个听力测试，可以精确评估用于研究人类听觉障碍的斑马鱼突变体的听力缺陷。其次，PI将研究野生型斑马鱼的听觉功能如何在受精后的早期发育期间增强。最佳频率，最佳灵敏度和听觉频率范围的时间表将确定几个不同年龄段的斑马鱼，从孵化到成年。 PI将确定听力功能发展的关键时期，并确定听觉能力达到高原的时间。我们对年轻的幼虫斑马鱼可以听到的声音以及其听觉功能的发展知之甚少。这项研究的结果将填补这一知识差距，以进一步建立斑马鱼作为听觉研究的模型系统。受精后，斑马鱼胚胎的易于访问性使斑马鱼成为研究脊椎动物早期听力发育的理想候选者。这项研究的结果将有助于我们更好地了解包括人类在内的脊椎动物中听觉功能的早期发展的演变。该项目开发的方法将使斑马鱼研究界能够精确评估用于研究人类听力障碍的斑马鱼突变体的听觉功能缺陷，并有助于进一步建立斑马鱼作为人类听力研究的脊椎动物模型系统。这项研究的结果将填补幼虫斑马鱼的听觉能力的知识差距，并洞悉包括人类在内的脊椎动物中听觉功能的早期发展的进化。