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.

项目摘要： 声音本地化 - 确定声音中的空间位置 - 是听觉系统的基础任务。 虽然在发现调解声音的基本神经过程方面取得了很多进展 本地化，仍然存在很大的差距，以限制我们对基础电路的理解。我们在这里 专注于声音定位电路的一个关键组成部分，即 梯形体（MNTB）及其抑制输出。 该提议的总体假设是快速MNTB抑制对于神经是必不可少的 在两个声音主定位核上的ITD和IID计算，内侧和侧向上橄榄 （分别为MSO和LSO）。此外，我们建议MNTB抑制作用将具有足够的效果 关于听觉脑干响应（ABR）的Wove III的产生，使MNTB的抑制作用将 改变这一波。 ABR是一种非侵入性测量体内脑干神经元活性的方法，而 我们专注于第三波，因为在啮齿动物中，这种波通常与声音中神经元的活性有关 定位核。 为了检验假设，我们将在光遗传学上操纵MNTB并记录MSO活动以区分 在MSO神经元的几种竞争声音定位模型之间（AIM 1）。然后我们将光学 操纵MNTB并记录低频LSO活性，以研究低频LSO神经元人群 （目标2）。最后，我们将光遗传学抑制MNTB，并记录对ABR的响应和影响（AIM 3）。 这种操纵模仿了影响双耳听力的常见听力条件下的类似ABR改变。 总体而言，目的旨在增强我们对听觉中声音定位机制的理解 脑干，大脑区域，根据他们 空间位置。在许多医疗条件中，此途径的改变导致 患者在噪声环境中定位声音和功能的能力降低。更好地理解 在健康听觉系统中，该电路中的神经机制将有助于设计这些治疗 未来的条件。