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Glia as regulators of auditory nerve function

神经胶质细胞作为听觉神经功能的调节者

基本信息

批准号：
BB/M019322/1
负责人：
Daniel Jagger
金额：
$ 48.65万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FM019322%2F1
关键词：
Glia regulators auditory nerve function

项目摘要

Mammals have an extraordinary ability to analyse the sounds within their environment and this can provide them with important advantages for survival. Humans hearing appears best-tuned to the range of sound frequencies that are used for speech-based communication, and this is also relevant for our appreciation of music. The sensory organ of hearing, the "cochlea", analyses incoming sound waves and sends electrically coded signals to the brain via groups of excitable cells within the auditory nerve. All the necessary information we require to understand the pitch, loudness, site of origin of sounds etc, are carried within the fine detail of the electrical code that the nerve passes to the brain. The nerve cells are able to work continually, at very high rates, and for many years without being replaced, because the environment they inhabit is kept stable by non-sensory cells called "glia". There is evidence from elsewhere in the nervous system that there is continual communication between nerve cells and their attendant glia, and that this can inform glia to be reactive to changes in nerve activity. The details of how this happens in the cochlea are unknown. Failures of this nerve-glia communication are suggested to cause death of nerve cells and conditions such as chronic pain. Glia are also responsible for coating the nerve cells with an insulating layer called "myelin". Myelin acts like the plastic coating on household wires, to improve electrical conductivity and to minimise energy losses as signals are carried over long distances. It is thought that the way in which myelin is laid down during development acts as an important cue for the maturation of nerve function. This has important implications for our understanding of the onset of sensory function in humans, and is particularly relevant to how hearing develops. This project is aimed towards a better understanding of glial function in the cochlea, and how glia preserve essential signalling in the auditory nerve. The data from this study would help explain some of the complexities of normal hearing, and may identify potential targets for therapies aimed at enhancing nerve cell survival in the inner ear. In addition the project would assist in the future design of devices such as cochlear implants. In some people who have lost their hearing the glia ensure the survival of some of the nerve cells in the deafened ear, even for years after deafness first occurs. This survival means the nerves can be electrically stimulated via a cochlear implant, providing the profoundly deaf with some hearing. Glia are clearly important in both the hearing and deaf ear, but it is not currently obvious how they carry out these essential roles. The findings of the study would not be specific to hearing though, as many of the mechanisms to be studied are common throughout the nervous system. A more comprehensive picture of how glial cells function would be of value to other scientists and clinicians studying the nervous system, including the other sense organs and the brain.

哺乳动物具有分析环境中声音的非凡能力，这可以为它们的生存提供重要的优势。人类的听觉似乎最适合用于语音交流的声音频率范围，这也与我们对音乐的欣赏有关。听觉的感觉器官--“耳蜗”--分析传入的声波，并通过听神经内的一组可兴奋的细胞向大脑发送电子编码信号。我们理解音调、响度、声音来源等所需的所有必要信息，都包含在神经传递给大脑的电码的细节中。神经细胞能够以非常高的速度持续工作，并持续多年而不被取代，因为它们所居住的环境是由称为“神经胶质”的非感觉细胞保持稳定的。来自神经系统其他地方的证据表明，神经细胞和伴随它们的神经胶质细胞之间有持续的通讯，这可以让神经胶质细胞对神经活动的变化做出反应。这是如何在耳蜗里发生的细节还不得而知。这种神经-胶质细胞通讯的失败被认为是导致神经细胞死亡和慢性疼痛等情况的原因。神经胶质细胞还负责在神经细胞上覆盖一层名为“髓鞘”的绝缘层。髓磷脂的作用就像家用线上的塑料涂层，提高了导电性，并在信号远距离传输时将能量损失降至最低。人们认为，髓鞘在发育过程中的形成方式是神经功能成熟的重要线索。这对于我们理解人类感觉功能的开始有重要的意义，特别是与听力如何发展有关。这个项目的目的是为了更好地了解耳蜗神经胶质细胞的功能，以及神经胶质细胞如何保存听神经中的基本信号。这项研究的数据将有助于解释正常听力的一些复杂性，并可能确定旨在增强内耳神经细胞存活的治疗的潜在靶点。此外，该项目还将协助今后设计人工耳蜗等设备。在一些听力丧失的人中，胶质细胞确保了耳聋患者耳朵中的一些神经细胞的存活，即使在耳聋首次发生后的几年也是如此。这种存活意味着神经可以通过植入人工耳蜗电刺激，为深度失聪的人提供一些听力。胶质细胞显然对听力和聋耳都很重要，但目前还不清楚它们是如何发挥这些重要作用的。然而，这项研究的结果并不是专门针对听力的，因为许多将要研究的机制在整个神经系统中都是常见的。更全面地了解神经胶质细胞的功能，对于研究神经系统(包括其他感觉器官和大脑)的其他科学家和临床医生来说是有价值的。