Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus

项目摘要 巨大的噪音和传导性听力损失都会对听力产生长期的有害影响。可能的 机制主要是在听觉通路的高阶阶段研究的，但早期的影响 途径相对未知，尽管那里的变化可能会对所有人产生影响 下游加工。我们发现，声音驱动的活动触发了一种新的、缓慢的适应机制 这改变了听神经突触的性质，这些突触位于中枢听觉的最开始 路径。在一周内暴露在增强的声音环境中，听觉神经突触 减少抑制和扩张结构，以及增强突触后丛状细胞的尖峰， 它们结合在一起可以增强对突触驱动活动的保真度。相比之下，在一周的闭塞之后， 耳道，听神经突触增加了抑制和缩小的大小，减少了尖峰和 在茂密的牢房里保持忠诚。这些变化令人惊讶，因为长期以来人们一直认为早期的听觉 路径不受感官体验的影响，除非在极端的病理条件下。这引发了 这一机制可能与耳鸣和中耳炎等疾病有关。因此，它是 重要的是要了解这种机制通常是如何触发的，以及它背后的机制是什么。目标1 将检查听觉神经突触对异常声级的敏感性，根据年龄和 暴露的持续时间。目标2将使用体外方法来揭示这些变化背后的机制 突触功能。目标#3将在体外和体外研究突触保真度的功能后果 活着。研究这一机制将导致对突触正常调控方式的新理解，因为 以及治疗活动异常引起的疾病的新疗法，包括耳鸣和中耳炎。

Project Summary Both loud noise and conductive hearing loss can have long-term detrimental effects on hearing. The possible mechanisms have primarily been studied at high-order stages of the auditory pathway, but effects early in the pathway are relatively unknown, despite the likelihood that changes there could have consequences for all downstream processing. We found that sound-driven activity triggers a novel, slow adaptation mechanism that alters the properties of auditory nerve synapses, which are at the very start of the central auditory pathway. Within a week’s exposure to an augmented sound environment, auditory nerve synapses have reduced depression and expanded structure, as well as enhanced spiking in the postsynaptic bushy cells, which combine to enhance fidelity to synaptically-driven activity. By contrast, after one week of occluding the ear canal, auditory nerve synapses have increased depression and reduced size, with reduced spiking and fidelity in bushy cells. These changes are surprising, because it has long been thought that the early auditory pathway was unaffected by sensory experience, except under extreme, pathological conditions. This raises the possibility that this mechanism could be involved in disorders such as tinnitus and otitis media. Therefore, it is important to understand how this mechanism is normally triggered and what mechanisms underlie it. Aim #1 will examine the susceptibility of auditory nerve synapses to abnormal sound levels, in terms of age and duration of exposure. Aim #2 will use in vitro methods to uncover the mechanisms underlying the changes in synaptic function. Aim #3 will examine the functional consequences for synaptic fidelity, both in vitro and in vivo. Studying this mechanism will lead to new understanding of how synapses are normally regulated, as well as new treatments for disorders caused by abnormal activity, including tinnitus and otitis media.