Cellular Mechanisms of Binaural Hearing Neurons in an Avian Interaural Level Difference Circuit

鸟类耳间电平差电路中双耳听觉神经元的细胞机制

• 批准号: 9318121
• 负责人: Rebecca Curry
• 金额: $ 0.44万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318121
• 关键词: Acoustics; Action Potentials; Affect; Anatomy; Animal Model; Animals; Auditory; Auditory system; Behavior; Behavioral; Behavioral Research; Binaural; Birds; Brain; Brain Stem; Cell Nucleus; Cell model; Cells; Cellular Morphology; Characteristics; Chickens; Closure by clamp; Cochlea; Cochlear Implants; Cochlear nucleus; Code; Complex; Computer Systems; Contralateral; Cues; Data; Development; Dorsal; Electrodes; Electrophysiology (science); Environment; Evolution; Foundations; Frequencies; Glutamates; Glycine; Human; Immunohistochemistry; Impairment; In Vitro; Individual; Injection of therapeutic agent; Interneurons; Knowledge; Lateral Dorsal Nucleus; Lateral lemniscus; Location; Mammals; Medial; Modeling; Molecular; Morphology; Nervous system structure; Neurons; Neurotransmitters; Patients; Pattern; Pharmacology; Physiological; Physiology; Population; Property; Research; Resistance; Slice; Sound Localization; Source; Synapses; Synaptic Transmission; System; Testing; Time; Work; auditory nuclei; auditory processing; base; binaural hearing; cell type; comparative; gamma-Aminobutyric Acid; hearing impairment; histological studies; in vivo; insight; neural circuit; new technology; novel strategies; prevent; response; sound; synaptic inhibition; tool; transmission process; voltage

Project Summary Humans and animals rely on sound localization to communicate and survive in complex acoustic environments. The auditory periphery (cochlea), however, does not encode the location of sound. Instead, the central auditory system computes horizontal sound location by encoding binaural cues such as interaural time and level difference (ITD and ILD). Despite the valuable insight that comparative work of ITD coding between mammals and birds has produced for understanding human auditory processing, there is a gap in knowledge for the cellular mechanisms of ILD coding in birds, limiting our understanding of the range of possible coding strategies and circuitry development for sound localization. Because sound localization ability is diminished in humans with hearing impairments and those with cochlear implants, identifying new mechanisms for ILD coding may inspire new technologies and approaches to restore sound localization ability. Avian models have been essential for developing the principles of sound localization coding and have produced a strong framework for understanding human auditory processing. In birds, the first central auditory nucleus encoding ILD is the posterior portion of the dorsal nucleus of the lateral lemniscus (LLDp; formerly VLVp, nucleus ventralis lemnisci lateralis pars posterior). Previous in vivo and histological studies have shown that LLDp neurons receive excitatory inputs from the contralateral cochlear nucleus, as well as inhibitory inputs from the other LLD. However, little is known about the specialized physiological and morphological properties of LLDp neurons that enable them to encode ILD. To determine the cellular mechanisms underlying ILD coding in the avian ILD circuitry, in vitro slice electrophysiology will be used to record from individual neurons in the chicken LLDp. The proposed work will test three hypothetical models to determine whether the LLDp encodes ILD through the use of (A) interneurons, (B) one principal cell population, or (C) two principal cell populations, and determine the specializations needed to support the circuit. Aim 1 will determine the intrinsic neuronal properties of LLDp neurons, such as action potential firing patterns will establish the criteria for identifying cell types for the next two aims. Aim 2 will characterize the synaptic properties of excitatory and inhibitory transmission in the LLDp and establish a working cellular model for ILD coding in birds. Aim 3 will identify individual cell morphology, neurotransmitter utilization, and projections between the two LLDs to determine how the anatomy of the LLDp relates to its physiology. The results are expected to establish a working cellular model for avian ILD coding, provide foundational interpretations for avian in vivo physiological and behavioral research, and advance our understanding of the cellular mechanisms underlying synaptic inhibition in auditory processing.

项目摘要 人类和动物依靠声音定位在复杂的声学环境中进行交流和生存 环境.然而，听觉外围（耳蜗）并不编码声音的位置。而是 中央听觉系统通过对双耳线索进行编码 和水平差异（ITD和ILD）。尽管有价值的见解，比较工作的ITD编码之间 哺乳动物和鸟类已经产生了理解人类的听觉处理，在知识上存在差距 对于鸟类ILD编码的细胞机制，限制了我们对可能编码范围的理解 声音定位的策略和电路开发。由于声音定位能力减弱， 人类听力障碍和人工耳蜗植入者，确定ILD的新机制 编码可以激发新的技术和方法来恢复声音定位能力。 鸟类模型对于发展声音定位编码的原理至关重要， 为理解人类听觉处理过程提供了一个强有力的框架。鸟类的第一听觉中枢 编码ILD的核是外侧丘系背核的后部（LLDp;以前 VLVp，腹侧丘系外侧核后部）。先前的体内和组织学研究表明， LLDp神经元接受来自对侧耳蜗核的兴奋性输入以及抑制性输入 另一个LLD。然而，很少有人知道的专门生理和形态学特性 使它们能够编码ILD。确定ILD编码的细胞机制 在禽类ILD电路中，体外切片电生理学将用于记录来自单个神经元的 鸡LLDp。拟议的工作将测试三个假设的模型，以确定是否LLDp编码 通过使用（A）中间神经元，（B）一个主要细胞群，或（C）两个主要细胞群， 并确定支持电路所需的专业化。 目的1将确定LLDp神经元的内在神经元特性，如动作电位放电 模式将为接下来的两个目标建立识别细胞类型的标准。目标2将描述 LLDp中兴奋性和抑制性传递的突触特性，并建立工作细胞模型 用于鸟类ILD编码。目标3将确定单个细胞形态，神经递质的利用， 两个LLD之间的投影以确定LLDp的解剖结构如何与其生理学相关。的 本研究结果有望建立禽类ILD编码的细胞模型，为进一步研究禽类ILD的分子生物学机制提供基础。 解释鸟类在体内的生理和行为研究，并推进我们对 听觉处理中突触抑制的细胞机制。