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

声音是由位于内耳的极其敏感的感觉细胞(称为毛细胞)探测到的。毛细胞传递声学信息(如频率和强度)，并将其转换为电信号，通过听神经纤维发送到大脑。这让我们可以交流和欣赏音乐。我们目前关于耳蜗毛细胞如何运作的知识来自于体外实验，因为从完整的哺乳动物耳蜗亚细胞分辨率进行体内测量长期以来一直被认为是不可行的。这对我们理解耳蜗的发育和功能造成了很大的障碍，因为体外工作不能复制它复杂的解剖学、神经和生理学。这个博士项目的目的是了解在体内发育中的哺乳动物耳蜗自发放电活动的调节和模式的机制，以及这些机制如何影响中枢听觉的精炼。这项提议将要求学生进行实验室中成熟的最先进的技术，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)，将使学生能够通过监测单个细胞和突触的活动来研究发育中的耳蜗的功能变化。

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.