Changes of temporal coding in inferior colliculus and auditory cortex of the guinea pig after cochlear lesion

本课题将研究损伤耳蜗区(内耳的听觉部分)高频区后，下丘(IC)和听觉皮质(AC)低频区神经元时间编码的变化。以往的研究表明，耳蜗病的影响不仅限于听觉外周，还延伸到中枢听觉系统(CAS)。因此，在CAS患者中，声音的频率、强度和时间特征的可塑性变化与感音神经性听力损失(SNHL)有关。然而，对于SNHL引起的时间加工问题，目前还没有一个全面的理解。具体来说，目前尚不清楚高频SNHL这一老年人最常见的SNHL模式是否会像强度和频率编码那样对低频区域的时间加工产生“离道”影响。这将是拟议研究的重点。IC和AC神经元的临时编码行为将在刺激前时间直方图(PSTH)中测量，在对幅度调制(AM)和间隙的反应中，以及在时长调整中。耳蜗病的效果将通过两种方法来评估：(1)通过比较短时间暴露于被研究神经元频率-响应区以外的高频创伤音前后的神经元反应；(2)通过比较正常受试者和使用噪声创伤或耳毒性药物在高频区造成慢性耳蜗病的神经元的时间编码。我们还将探索使用植入的微电极来观察永久性耳蜗病后可塑性的动态发展。此外，我们将研究AM反应在IC和AC中的稳健性，这种反应对AM的持久性对背景噪声的影响，局部抑制在这种持久性中的作用，以及最后高频耳蜗病对这种持久性的潜在影响。

This project will investigate the changes of temporal coding of neurons in low frequency region of inferior colliculus (IC) and auditory cortex (AC) after damage is created in high frequency region in cochleae (the auditory part of inner ears). Previous studies have suggested that the impact of cochlear lesion is not confined to the auditory peripheral, but extends to central auditory system (CAS) as well. Consequently, plastic changes in the processing of frequency, intensity as well as temporal features of sound have been associated in CAS with sensorineural hearing loss (SNHL). However, a comprehensive understanding in temporal processing problem due to SNHL is not available. Specifically, it is not clear whether and how high-frequency SNHL, the most common pattern of SNHL for the elderly, will produce "off-channel" impact on the temporal processing in the low-frequency region as it has been demonstrated in intensity and frequency coding. This will be the focus of the proposed study.Temporal coding behaviours of IC and AC neurons will be measured in peristimulus time histogram (PSTH), in responses to amplitude modulation (AM) and gaps, as well as in duration tuning. The effect of cochlear lesion will be evaluated in two approaches: (1) by comparing the neuronal responses before and after a short exposure to a traumatizing tone of a high frequency beyond the frequency-response region of the neuron that is under study, (2) by comparing the neurons' temporal coding between normal subjects and those with the chronic cochlear lesion created in high-frequency region by using noise trauma or ototoxic drugs. We will also explore the use of implanted microelectrode to observe the dynamic development of plasticity after a permanent cochlear lesion. In addition, we will investigate the robustness of AM response in IC and AC, the persistence of this response to AM against background noise, the role of local inhibition in this persistence, and finally the potential impact of high-frequency cochlear lesion on this persistence.