Mechanisms of Auditory Circuit Development

听觉回路发育的机制

• 批准号: 10530698
• 负责人: Ulrich Mueller
• 金额: $ 67.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530698
• 关键词: Affect; Afferent Neurons; Anatomy; Auditory; Auditory Perception; Cell Communication; Child; Data; Defect; Development; Disease; Electrophysiology (science); Felis catus; Fluorescence; Genes; Genetic; Genomics; Goals; Hair Cells; Health; Hearing; Hearing Tests; Histology; Human; Image; Individual; Inner Hair Cells; Laboratories; Link; Maps; Measures; Molecular; Molecular Profiling; Mus; Mutation; Neuronal Differentiation; Neurons; Outer Hair Cells; Pattern; Play; Presbycusis; Property; Publications; Publishing; Quality of life; Regulation; Reporter; Sense Organs; Signal Transduction; Tamoxifen; Testing; Tinnitus; Wild Type Mouse; Work; aging population; deafness; genetic manipulation; genomic tools; hearing impairment; inducible Cre; insight; nerve supply; postnatal; single-cell RNA sequencing; sound; spiral ganglion

PROJECT SUMMARY The long-term goal of my laboratory is to elucidate the mechanisms that regulate auditory perception, and how defects in hair cells and auditory neurons cause disease. We propose here to study the mechanisms that regulate the differentiation, connectivity and function of spiral ganglion neurons (SGNs). Our central hypothesis is that SGNs are a diverse group of neurons with different connectivity patterns and functions, and that diversification of SGNs and their connectivity depends on signals provided by hair cells. To test our hypothesis, we will combine studies in genetically modified mice with histology, imaging, genomics, electrophysiological and hearing tests to study SGN connectivity and function. We will map SGN projection patterns, define how mutations linked to deafness affect SGN differentiation and projection patterns, and use genetic manipulations combined with electrophysiology and genomic tools to identify signals initiated by hair cells that affect SGN differentiation. Our preliminary data show the feasibility of our approach, demonstrating that SGNs are a molecularly diverse group of neurons with different projection patterns and that defect in hair cells affect SGN differentiation. We anticipate that our findings will define mechanisms by which hair cells affect SGNs to regulate their diversification into subtypes with different functions and connectivity patterns.

项目概要 我实验室的长期目标是阐明调节听觉感知的机制，以及如何 毛细胞和听觉神经元的缺陷会导致疾病。我们在这里建议研究调节机制 螺旋神经节神经元 (SGN) 的分化、连接性和功能。我们的中心假设是 SGN 是一组不同的神经元，具有不同的连接模式和功能，并且多样化 SGN 的结构及其连接性取决于毛细胞提供的信号。为了检验我们的假设，我们将结合 通过组织学、成像、基因组学、电生理学和听力测试对转基因小鼠进行研究 研究 SGN 连接性和功能。我们将绘制 SGN 投影模式，定义突变如何关联到 耳聋影响 SGN 分化和投射模式，并结合基因操作 电生理学和基因组工具可识别毛细胞发出的影响 SGN 分化的信号。我们的 初步数据显示了我们方法的可行性，证明 SGN 是一个分子多样化的群体 具有不同投射模式的神经元以及毛细胞的缺陷会影响 SGN 的分化。我们预计 我们的研究结果将定义毛细胞影响 SGN 的机制，从而调节其多样化 具有不同功能和连接模式的亚型。