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

项目摘要 人类和动物依靠声音本地化在复杂的声学环境中交流和生存 环境。然而，听觉外周(耳蜗)并不编码声音的位置。相反， 中央听觉系统通过编码双耳提示(如耳间时间)来计算水平声音位置 和水平差异(ITD和ILD)。尽管ITD编码的比较工作具有重要的洞察力 哺乳动物和鸟类已经产生了对人类听觉加工的理解，存在着知识上的空白 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 声音本地化的策略和电路开发。因为声音定位能力在 患有听力障碍的人类和植入人工耳蜗者，确定ILD的新机制 编码可能会启发新的技术和方法来恢复声音定位能力。 禽类模型对于发展声音定位编码的原则是必不可少的，并已 为理解人类的听觉处理提供了一个强大的框架。鸟类的第一个中枢听觉 编码ILD的核是外侧丘系背核的后部(LLDP；以前 VLVp，丘疹外侧侧部腹侧核)。先前的活体和组织学研究表明 LLDP神经元接受来自对侧耳蜗核的兴奋性输入和抑制性输入 来自另一个LLD。然而，人们对其特殊的生理和形态特征知之甚少。 使它们能够编码ILD的LLDP神经元。确定ILD编码背后的细胞机制 在禽类ILD电路中，体外切片电生理学将被用来记录 鸡肉自民党。拟议的工作将测试三个假设模型，以确定LLDP是否编码 ILD通过使用(A)中间神经元，(B)一个主细胞群，或(C)两个主细胞群， 并确定支持电路所需的专业化认证。 Aim 1将确定LLDP神经元的固有神经元特性，如动作电位放电 模式将建立识别下两个目标的细胞类型的标准。目标2将描述 LLDP兴奋性和抑制性传递的突触特性及工作细胞模型的建立 用于鸟类的ILD编码。目标3将确定单个细胞的形态，神经递质的利用，以及 两个LLD之间的投影，以确定LLDP的解剖与其生理之间的关系。这个 研究结果可望建立禽类ILD编码的工作细胞模型，为禽类ILD编码提供基础 对鸟类体内生理和行为研究的解释，并增进我们对 听觉加工中突触抑制的细胞机制。

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.