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

识别复杂声音和声音定位需要具备跟踪高频率声音的时间结构的能力。中枢性听觉障碍（central auditory disorder， CAPD）以正常的耳蜗阈值为特征，但影响对声音的识别、辨别、分离、分组、定位或排序。为了研究CAPD的病理生理机制，并开发一种临床可开发的病因鉴别诊断方法，我们将使用诱导脑干cav1.3缺失的转基因小鼠。初步结果显示，这些动物的听力阈值正常，脑干诱发反应（ABRs）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。下丘是最核心的听觉结构，在转基因动物中，与声音输入和接收来自受影响结构的输入的时间同步表现出高度的精度。我们想测试神经元跟随声音的时间包络的能力。此外，还将研究方位位置的线索。最后，abr将在时间复杂的声音刺激下被记录下来。在确定中脑缺陷的神经元特征后，将设计一种刺激，可以使用人类受试者的abr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.