Neural coding of sound location under normal and impaired hearing conditions

描述(由申请人提供)：用于在水平面(即方位)定位声音的双耳线索以及这些线索在中枢听觉系统神经元的反应中被编码的神经机制是众所周知的。目前尚不清楚的是，对ITD和ILD敏感的神经元的组合反应如何形成对自然听觉场景的变化具有健壮性的方位位置的神经表示。本研究主要研究下丘(IC)神经元群体对声源方位角的编码变化：1)声级变化；2)竞争声源的存在。第三个目的是研究感音神经性耳聋(SNHL)对方位角群体编码的影响。这些目标将通过从清醒兔的IC中的单个单元记录中收集方位调谐函数来实现。种群IC响应将被用于训练和测试源方位角的最大似然解码器，作为评估种群活动的方位编码能力的手段，并测试特定于源方位的种群活动模式是否对其他声音参数(例如，声级)的变化具有健壮性。目标1中的实验将使用在多个声级收集的方位调谐函数来测试解码器的性能是否与声级不变；或者换句话说，跨IC神经元(或神经元亚群)的特定位置的活动模式在不同声级之间是否保持基本相似。目标2中的实验将研究在具有不同声源起点的多源环境中声音位置的神经编码。当一个声源先于另一个声源开始时，IC神经元可能会适应较早的声源，并为较晚到达的声源“揭开”方位信息。为了验证这一假设，将收集单独目标和目标加干扰条件下的方位调谐函数(同时和起始差)。解码器将被用来评估IC活动模式的不变性，当在单独的目标数据上进行训练并在目标加干扰数据上进行测试时。最后，目标3的实验将测试患有双侧SNHL的兔的IC神经元的方位编码是否退化--SNHL是永久性听力损失的主要形式。通过高强度噪声暴露诱导兔SNHL。在暴露两周后证实永久性听力损失后，将在IC中测量方位调谐功能。将比较暴露在噪声中的兔和未暴露的兔之间的译码性能，以评估SNHL后IC神经元对源方位编码的能力是否下降。方位调谐也将在只有耳间时间差或耳间电平差随方位角变化的情况下进行测量，以评估任何特定缺陷I双耳线索的神经表示。

DESCRIPTION (provided by applicant): The binaural cues used to localize sound in the horizontal plane (i.e., azimuth) and the neural mechanisms by which these cues are encoded in the responses of neurons in the central auditory system are well known. What remains unclear is how the combined responses across neurons that are sensitive to ITD and ILD form a neural representation of azimuthal location that is robust to changes in natural auditory scenes. This proposal focuses on how the population response of neurons in the inferior colliculus (IC) encodes sound source azimuth with respect to two of these changes: 1) with changes in sound level, and 2) in the presence of a competing sound source. The third aim investigates changes in the population encoding of azimuth brought about by sensorineural hearing loss (SNHL). These aims will be addressed by collecting azimuth tuning functions from single-unit recordings in the IC of awake rabbits. Population IC responses will be used to train and test a maximum-likelihood decoder of source azimuth as a means to both evaluate the azimuth encoding ability of population activity, and to test whether patterns of population activity specific to source azimuth are robust to changes in other sound parameters (e.g., sound level). Experiments in Aim 1 will use azimuth tuning functions collected at multiple sound levels to test whether performance of the decoder is invariant to sound level; or in other words, whether the location-specific patterns of activity across IC neurons (or a subpopulation of neurons) remain largely similar between sound levels. Experiments in Aim 2 will investigate the neural coding of sound location in a multisource environment with different sound source onsets. When the onset of one sound source precedes another, IC neurons may adapt to the early-onset source and "unmask" azimuth information for the later arriving source. To test this hypothesis, azimuth tuning functions will be collected under target-alone and target-plus-interferer conditions (both simultaneous and onset difference). The decoder will be used to assess invariance of IC activity patterns when trained on target-alone data and tested on target-plus- interferer data. Finally, experiments in Aim 3 will test whether or not the azimuth encoding of IC neurons is degraded in rabbits with bilateral SNHL-the leading form of permanent hearing loss. SNHL will be induced in rabbits via high-level noise exposure. Following verification of permanent hearing loss two weeks after exposure, azimuth tuning functions will be measured in the IC. Decoder performance will be compared between noise-exposed rabbits and unexposed rabbits to evaluate whether there is a decrease in the ability of IC neurons to encode source azimuth following SNHL. Azimuth tuning will also be measured under conditions where only interaural time difference or interaural level difference varies with azimuth to assess any specific deficit i the neural representation of either binaural cue.