In vivo investigation of spontaneous activity in the prehearing mammalian auditory system

哺乳动物听力前听觉系统自发活动的体内研究

• 批准号: 2881096
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2881096
• 关键词: vivo; investigation; spontaneous; activity; prehearing

Sound is detected by extremely sensitive sensory cells, called hair cells, located in the inner ear. Hair cells transduce acoustic information (e.g. frequency and intensity) and convert them into electrical signals that are sent to the brain via auditory nerve fibres. This allows us to communicate and enjoy music.Our current knowledge of how hair cells in the cochlea operate derive from ex vivo experiments, since in vivo measurements with subcellular resolution from the intact mammalian cochlea have long been considered unfeasible. This has created a substantial barrier towards our understanding of how the cochlea develop and function, since ex vivo work cannot replicate its sophisticated anatomy, innervation and physiology.The aim of this PhD project is to understand the mechanisms that modulate and pattern the spontaneous firing activity in the developing mammalian cochlea in vivo, and how these influence central auditory refinement. This proposal will require the student to perform state-of-the-art techniques that are well established in the lab, including in vivo 2-photon functional imaging and in vivo AAV-gene delivery, applied to transgenic mice. These experimental approaches, combined with large data analysis (MATLAB and/or Python), will allow the student to investigate functional changes in the developing cochlea by monitoring the activity of individual cells and synapses.

声音是由位于内耳的极其敏感的感觉细胞——毛细胞探测到的。毛细胞将声音信息（例如频率和强度）转换成电信号，通过听觉神经纤维发送到大脑。这使我们能够交流和享受音乐。我们目前对耳蜗毛细胞如何运作的了解来自于离体实验，因为对完整的哺乳动物耳蜗进行亚细胞分辨率的体内测量长期以来被认为是不可行的。这对我们理解耳蜗的发育和功能造成了很大的障碍，因为离体研究无法复制其复杂的解剖结构、神经支配和生理。本博士项目的目的是了解哺乳动物体内耳蜗自发放电活动的调节和模式机制，以及这些活动如何影响中枢听觉细化。该提案将要求学生在实验室中使用最先进的技术，包括应用于转基因小鼠的体内双光子功能成像和体内aav基因传递。这些实验方法，结合大数据分析（MATLAB和/或Python），将允许学生通过监测单个细胞和突触的活动来研究耳蜗发育中的功能变化。