Mechanisms of Auditory Circuit Development

项目摘要 我实验室的长期目标是阐明调节听觉感知的机制，以及如何调节听觉感知。 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 螺旋神经节神经元的分化、连接和功能。我们的核心假设是， SGN是一组具有不同连接模式和功能的多样化神经元， SGN的形成和连接依赖于毛细胞提供的信号。为了验证我们的假设，我们将联合收割机 对转基因小鼠进行组织学、成像、基因组学、电生理学和听力测试， 研究SGN连通性和功能。我们将绘制SGN投影模式，定义突变如何与 耳聋影响SGN分化和投射模式，并使用遗传操作结合 电生理学和基因组工具来鉴定由毛细胞引发的影响SGN分化的信号。我们 初步数据显示了我们方法的可行性，证明SGN是一个分子多样性的群体 不同投射模式的神经元的分化以及毛细胞的缺陷影响SGN的分化。我们预计 我们的研究结果将确定毛细胞影响SGN的机制，以调节它们的多样化， 具有不同功能和连接模式的子类型。

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.