Fast temporal processing and ,central auditory disorder`: subcortical mechanisms

在高频下跟踪声音的时间结构的能力是辨别复杂声音和声音定位所必需的。中枢性听觉障碍(CAPD)的特征是耳蜗阈值正常，但会影响声音的识别、辨别、分离、分组、定位或排序。为了研究CAPD的病理生理学机制，并开发一种临床上可用于鉴别诊断病因的方法，将使用脑干诱导Cav1.3缺陷的转基因小鼠。初步结果显示，这些动物听力阈值正常，脑干诱发反应(ABR)异常，脑干结构改变，符合CAPD的定义。在本项目中，将研究这些动物的下丘神经元对简单音调、复杂声音和双耳刺激的反应。下丘是最中央的听觉结构，在时间上与声音输入和从转基因动物受影响的结构接受输入的时间同步显示出很高的精度。我们想测试神经元跟随声音时间包络的能力。此外，还将调查方位位置的线索。最后，在刺激过程中，将用时间复杂的声音来记录ABR。在确定了中脑缺陷的神经元特征后，将设计一种刺激，允许使用人类受试者的ABR来检测所描述的缺陷。

The ability to follow the temporal structure of sounds at high frequencies is required for discrimination of complex sounds and sound localization. The central auditory disorder (CAPD) is characterized by normal cochlear thresholds, but affected recognition, discrimination, separation, grouping, localization or ordering of sounds. To investigate the pathophysiology of CAPD and develop a clinically-exploitable method for differential diagnosis of the causes, transgenic mice with an induced Cav1.3-deficiency in the brainstem will be used. Preliminary results show that these animals have normal hearing thresholds, abnormal brainstem evoked responses (ABRs) and structural changes in the brainstem, corresponding to the definition of CAPD. In the present project, responses of neurons to simple tones, complex sounds and binaural stimuli will be investigated in the inferior colliculus of these animals. The inferior colliculus is the most central auditory structure showing a high precision in temporal synchrony with the acoustic input and receiving inputs from the structures affected in the transgenic animals used. We want to test the ability of neurons to follow the temporal envelope of the sounds. Also, the cues of azimuthal locations will be investigated. Finally, ABRs will be recorded during stimulation with temporally complex sounds. After determining the neuronal signature of the deficit in the midbrain, a stimulus will be designed that can allow to detect the described deficits using ABRs in human subjects.