Neural coding of sound location under normal and impaired hearing conditions

描述（由申请人提供）：用于在水平面中定位声音的双耳线索（即，方位角）和将这些线索编码在中枢听觉系统中的神经元的响应中的神经机制是众所周知的。目前尚不清楚的是，对ITD和ILD敏感的神经元之间的组合响应如何形成对自然听觉场景中的变化具有鲁棒性的方位角位置的神经表示。该建议的重点是下丘（IC）中的神经元的群体响应如何编码声源方位角相对于这些变化中的两个：1）声级的变化，以及2）在存在竞争声源的情况下。第三个目的是调查感音神经性听力损失（SNHL）带来的方位角编码的变化。这些目标将通过收集清醒家兔IC中单个单元记录的方位角调谐函数来实现。群体IC响应将用于训练和测试源方位角的最大似然解码器，作为评估群体活动的方位角编码能力以及测试特定于源方位角的群体活动模式是否对其他声音参数（例如，声级）。目标1中的实验将使用在多个声级下收集的方位角调谐函数来测试解码器的性能是否对声级不变;或者换句话说，跨IC神经元（或神经元的亚群）的位置特异性活动模式是否在声级之间保持很大程度上相似。目标2中的实验将研究在具有不同声源起始的多频环境中声音位置的神经编码。当一个声源先于另一个声源出现时，IC神经元可以适应早出现的声源，并“揭开”晚到达声源的方位角信息。为了检验这一假设，将在单独目标和目标加干扰条件下（同时和起始差异）收集方位角调谐函数。解码器将被用来评估IC活动模式的不变性时，训练的目标单独的数据和测试的目标加干扰数据。最后，目标3中的实验将测试在患有双侧SNHL（永久性听力损失的主要形式）的兔子中IC神经元的方位编码是否退化。将通过高水平噪声暴露在家兔中诱导SNHL。在暴露后两周验证永久性听力损失后，将在IC中测量方位角调谐功能。将在噪声暴露的兔子和未暴露的兔子之间比较解码器性能，以评估在SNHL之后IC神经元编码源方位角的能力是否降低。还将在仅耳间时间差或耳间水平差随方位角变化的条件下测量方位角调谐，以评估任一双耳线索的神经表征中的任何特定缺陷。

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.