Effect of IHC Loss on Auditory Function

描述（由申请人提供）：内毛细胞（IHC）和I型听觉神经纤维被认为是将听觉信息传递到中枢听觉系统的唯一途径;然而，对与仅限于IHC/I型神经元的损伤相关的听力和中枢听觉功能缺陷知之甚少。在灰鼠中，可以用抗癌药物沿着耳蜗的整个长度选择性地破坏IHC/I型神经元的子集沿着。这种类型的损伤造成了一种情况，其中中央听觉系统只接收到其正常神经输入的一小部分。哪些类型的听力障碍与IHC/I型病变相关？目前的建议将通过测量听力的五个不同方面来直接解决这个问题：（1）安静时听到长和短持续时间音调的阈值;这将评估系统和时间积分的灵敏度;（2）宽带噪声中音调检测的阈值;这将测试内部听觉滤波器的宽度和检测器机制的灵敏度，（3）窄带噪声的掩蔽模式;这评估了掩蔽对低频和高频的扩展，（4）强度鉴别和频率鉴别，以及（5）用于检测正弦幅度调制噪声的调制阈值，时间分辨率的综合测量。该项目还将记录下丘和听觉皮层的局部场电位，以观察阈值的神经相关性，强度的增加，噪声和窄带噪声掩蔽模式中音调的检测。听力功能和神经活动的变化将与IHC/I型神经元的损伤程度相关。该研究的结果可能对开发临床测试以检测患者的IHC/I型损伤以及了解听神经病（一种被认为涉及IHC或听神经病理的临床实体）具有重要意义。

DESCRIPTION (provided by applicant): The inner hair cells (IHC) and type-I auditory nerve fibers are thought to provide the only pathway through which auditory information is conveyed to the central auditory system; however, little is known about the deficits in hearing and central auditory function that are associated with damage that is exclusively confined to the IHC/type-I neurons. In the chinchilla, it is possible to selectively destroy a subset of IHC/type-I neurons along the entire length of the cochlea with an anticancer drug. This type of lesion creates a situation in which the central auditory system receives only a small percentage of its normal neural input. What types of hearing deficits are associated with an IHC/type-I lesion? The current proposal will determine directly address this question by measuring five different aspects of hearing: (1) thresholds for hearing long and short duration tones in quiet; this will assess the sensitivity of the system and temporal integration, (2) threshold for detection of tones in broadband noise; this will test the width of the internal auditory filters and the sensitivity of the detector mechanism, (3) masking patterns for narrow band noise; this assess the spread of masking to low and high frequencies, (4) intensity discrimination and frequency discrimination, and (5) modulation thresholds for detection sinusoid ally amplitude modulated noise, a comprehensive measure of temporal resolution. The project will also record the local field potentials from the inferior colliculus and auditory cortex to look at the neural correlates of threshold, increases in intensity, the detection of tones in noise and narrow band noise masking patterns. The changes in hearing function and neural activity will be correlated to the degree of damage to the IHC/type-I neuron. The results of the study could have important implications for developing clinical tests to detect IHC/type-I damage in patients and for understanding auditory neuropathy, a clinical entity thought to involve pathologies of the IHCs or auditory nerve.