Fast Inhibition in the Sound Localization Pathway

声音定位途径的快速抑制

• 批准号: 10570857
• 负责人: Achim Klug
• 金额: $ 35.22万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570857
• 关键词: Address; Affect; Area; Auditory; Auditory Brainstem Responses; Auditory system; Brain; Brain Stem; Cell Nucleus; Central Hearing Loss; Chlorides; Ear; Electrodes; Environment; Fiber Optics; Frequencies; Future; Generations; Gerbils; Halorhodopsins; Hearing; Hearing problem; Implant; Knock-out; Lead; Light; Location; Measures; Medial; Mediating; Medical; Methods; Modeling; Monitor; Neurons; Output; Pathway interactions; Patients; Play; Population; Process; Pump; Rodent; Role; Shapes; Sound Localization; Source; Testing; Time; age related; autism spectrum disorder; binaural hearing; design; experimental study; in vivo; lateral superior olive; medial superior olive; neural; neural circuit; neuromechanism; normal hearing; optical fiber; optogenetics; response; sound; sound frequency; therapy design; trapezoid body

Project Summary: Sound localization – determining where in space a sound originates – is a cardinal task of the auditory system. While much progress has been made in uncovering the fundamental neural processes that mediate sound localization, there still remain significant gaps that limit our understanding of the underlying circuit. Here we focus on the role played by one key component of the sound localization circuit, the medial nucleus of the trapezoid body (MNTB), and its inhibitory output. The overarching hypothesis of this proposal is that fast MNTB inhibition is essential for the neural computation of ITDs and IIDs at the two sound main localization nuclei, the medial and lateral superior olive (MSO and LSO, respectively). In addition, we propose that MNTB inhibition will have a sufficiently large effect on the generation of wave III of auditory brainstem responses (ABRs), such that suppression of MNTB will alter this wave. ABRs are a method that non-invasively measure in-vivo the activity of brain stem neurons, and we focus on wave III because in rodents this wave is commonly associated with activity of neurons in the sound localization nuclei. To test the hypothesis, we will optogenetically manipulate MNTB and record MSO activity to discriminate between several competing models of sound localization by MSO neurons (Aim 1). Then we will optogenetically manipulate MNTB and record low-frequency LSO activity to study a population of low-frequency LSO neurons (Aim 2). Finally, we will optogenetically suppress MNTB and record responses and effects on the ABR (Aim 3). This manipulation mimics similar ABR alterations in common hearing conditions affecting binaural hearing. Overall, the aims are designed to enhance our understanding of sound localization mechanisms in the auditory brainstem, the brain area that performs the first separation of multiple sounds from each other based on their spatial location. There are a number of medical conditions in which alterations in this pathway lead to a patient's decreased ability to localize sound and function in a noisy environment. A better understanding of the neural mechanisms in this circuit in the healthy auditory system will help design treatments for these conditions in the future.

项目概要： 声音定位——确定声音在空间中的来源——是听觉系统的一项基本任务。 尽管在揭示介导声音的基本神经过程方面已经取得了很大进展 本地化方面，仍然存在很大的差距，限制了我们对底层电路的理解。 重点关注声音定位回路的一个关键组成部分——内侧核——所扮演的角色。 梯形体（MNTB）及其抑制输出。 该提案的总体假设是，快速抑制 MNTB 对于神经系统至关重要 计算两个声音主要定位核（内侧和外侧上橄榄核）的 ITD 和 IID （分别是 MSO 和 LSO）。此外，我们认为 MNTB 抑制将产生足够大的效果。 听性脑干反应 (ABR) III 波的产生，从而抑制 MNTB 改变这种波是一种非侵入性测量体内脑干神经元活动的方法，并且 我们关注波 III，因为在啮齿动物中，该波通常与声音中神经元的活动相关 本地化核心。 为了检验这一假设，我们将通过光遗传学手段操纵 MNTB 并记录 MSO 活动以进行区分 MSO 神经元声音定位的几种竞争模型之间的比较（目标 1）然后我们将通过光遗传学方法。 操纵 MNTB 并记录低频 LSO 活动以研究低频 LSO 神经元群体 （目标 2）。最后，我们将通过光遗传学抑制 MNTB 并记录对 ABR 的反应和影响（目标 3）。 这种操作模仿了影响双耳听力的常见听力条件中类似的 ABR 变化。 总体而言，这些目标旨在增强我们对听觉中声音定位机制的理解 脑干，根据声音的不同，首先将多个声音相互分离的大脑区域 在许多医疗状况中，该通路的改变会导致空间位置的改变。 患者在嘈杂环境中定位声音和功能的能力下降。 健康听觉系统中该回路的神经机制将有助于设计针对这些问题的治疗方法 未来的条件。