Effect of Hearing Loss on the Properties of AVCN Neurons

由于损伤、疾病、衰老和其他因素，在成熟动物中缺乏活动的CNS神经元的电生理学后果的信息普遍缺乏。耳蜗核神经元的细胞特性变化与听力损失的关系尚不清楚。疾病和年龄相关的听力损失是一个普遍的问题，特别是在老龄化人口中。耳蜗植入研究的重点是如何设计人工设备，最好地模拟对声音刺激的听觉神经反应的编码，假设听力受损患者具有正常的耳蜗神经元功能，将忠实地将信息传输到更高的听觉中心。最近的研究表明，耳蜗电蚀后大鼠AVCN丛状细胞的静息膜电位升高，动作电位高度降低，后超极化降低，我们推测，AVCN丛状细胞作为听神经纤维的直接靶细胞，其生理特性的改变部分是由于低阈值钾电流和尚待表征的K（Ca）电导的改变。我们进一步假设，在神经丛细胞兴奋性突触受体亚单位（GluR 1 -4）的基因表达的变化也是由于听力损失的去神经。我们将采用多种电生理记录技术和定量RT PCR方法来验证我们的假设。这些研究将有助于阐明活动剥夺耳蜗核神经元生理后果的分子基础。

There has been a general lack of information regarding the electrophysiological consequences in activity deprived CNS neurons in mature animals due to injury, disease, aging and other factors. Little is known about the cellular property changes in cochlear nucleus neurons associated with hearing loss. Disease and age-related hearing loss is a prevalent problem especially among the aging population. Cochlear implant research has focused on how to engineer artificial devices that best simulate the coding of auditory nerve responses to sound stimuli with the assumption that hearing impaired patients have normal cochlear neuronal function that will faithfully transmit information to higher auditory centers. Recently it has been shown that bushy cells in cochlear ablated rats have elevated resting membrane potential and decreased action potential height and afterhyperpolarization, we hypothesize that these physiological property changes of AVCN bushy cells, the direct targets of auditory nerve fibers, are partly due to the change of the low- threshold potassium current and a yet to be characterized K(Ca) conductance. We further hypothesize that changes in gene expression of the excitatory synaptic receptor subunits (GluR1-4) in bushy cells are also the result of denervation due to hearing loss. We will employ a variety of electrophysiology recording techniques and quantitative RT PCR methods to test our hypotheses. These studies should shed light on the molecular basis of physiological consequences in activity deprived cochlear nucleus neurons.