Development of Temporal Fine structure

项目总结 拟议的研究计划的主要目标是促进我们对声音本地化的理解。连 当一个人的听力正常时，在嘈杂的混响环境中的言语感知和学习可能会 由于双耳听力能力持续受损，仍会受到损害。在更深刻的案例中 耳聋，双侧人工耳蜗者通常对耳间时差的辨别能力较差 (ITDS)，可能是由于早期剥夺。这项提案使用了一个鸟类模型来推进我们的 对双耳发展的理解。我们已经开发了这种制剂来确定是否/何时会有 每只耳朵的输入是同步的发育窗口，以便对ITDS敏感 发展。对双耳信号的敏感度首先出现在脑干，依赖于亚毫秒级的精度 检测ITDS。这种极端的精确度是如何在开发过程中产生的，目前还不能完全理解，这些 鸟类为精确定时双耳信号的测量提供了一个众所周知的模型。我们所了解的 这个ITD电路足够详细，足以测试以下关于生理和发育的假说 声音定位电路。在更广泛的背景下，理解声音本地化的机制应该 揭示常见的计算解决方案，以指导助听器和人工耳蜗设计的进步。这个 本项目要调查的三个重叠区域是： 1.确定在发育过程中ITDS的代表是否为塑料。 ITDS的检测依赖于对延迟的精确编码，目前的研究是ITDS如何随头部变化 成长。我们将使用单侧传导性听力损失(CHL)模型，在该模型中，一个耳道被堵塞 在听力开始前后，在头部发育期诱导经验依赖性可塑性。 这些实验应该可以让我们确定ITD的地图是否被早期的经验修改了。在AIM 1.2中 我们将重点研究髓鞘可塑性作为潜在的修饰机制。 2.解决时间精确度出现的潜在机制。 如果延迟可以通过改变的经验来改变，那么正常的ITD编码很可能也显示出发育 精致。延迟线以亚毫秒级的精度编码时间。以阐明这些机制 在ITD图形成的基础上，我们将结合细胞外场电位和细胞内场电位的记录 记录延迟线轴突，观察术后2个月ITD编码的发展情况。 3.抑制在ITD编码发展中的作用。 鉴于抑制在调节听觉脑干活动中的重要性，我们将研究 内侧核和耳蜗核的抑制性输入。我们将使用单边CHL模型来诱导经验 在ITD的MAP中的依赖可塑性，并检验目标1.2的竞争假设，延迟的变化是 与抑制的变化相关。

PROJECT SUMMARY The broad goal of the proposed research program is to advance our understanding of sound localization. Even when a person has normal hearing, speech perception and learning in noisy reverberant environments may still be compromised due to persistently impaired binaural hearing capabilities. In more profound cases of deafness, bilateral cochlear implant users typically experience poor discrimination of interaural time differences (ITDs), potentially because of early deprivation. This proposal uses an avian model to advance our understanding of binaural development. We have developed this preparation to determine if/when there is a developmental window in which inputs from each ear are synchronized, in order for sensitivity to ITDs to develop. Sensitivity to binaural signals first appears in the brainstem and relies on sub-millisecond precision to detect ITDs. How such extreme precision comes about during development is not fully understood, and these birds provide a well understood model for measurement of precisely timed binaural signals. Our knowledge of this ITD circuit is detailed enough to test the following hypotheses about the physiology and development of sound localization circuits. In the broader context, understanding the mechanisms of sound localization should reveal common computational solutions to guide advances in hearing aid and cochlear implant design. The three overlapping areas to be investigated in this project are: 1. Determine if the representation of ITDs is plastic during development. Detection of ITDs depends on precise coding of delay, with current research on how ITDs change with head growth. We will use a unilateral conductive hearing loss (CHL) model, in which one ear canal is plugged around the onset of hearing, to induce experience dependent plasticity during the period of head growth. These experiments should allow us to determine if maps of ITD are modified by early experience. In Aim 1.2 we will focus on myelin plasticity as a potential mechanism for modification. 2. Address mechanisms underlying the emergence of temporal precision. If delays can be modified by altered experience, it is likely that normal ITD coding also shows developmental refinement. Delay lines encode time with sub-millisecond accuracy. To shed light on the mechanisms underlying ITD map formation, we will combine recordings of the extracellular field potential with intracellular recording from delay line axons to measure the development of ITD coding in the first 2 months posthatch. 3. The role of inhibition in the development of ITD coding. Given the importance of inhibition in regulating auditory brainstem activity, we will examine the nature of the inhibitory input to NL and cochlear nuclei. We will use the unilateral CHL model to induce experience dependent plasticity in map of ITD, and test the competing hypothesis to Aim 1.2, that changes in delay are correlated with changes in inhibition.