Expression of Ion Channels in the Auditory System

描述：中枢听觉通路中神经元的放电模式编码 声音刺激的具体特征，如频率、强度和 空间定位。适当模式的生成取决于 在很大程度上，对电压依赖性钾通道的特性， 这些神经元。Shaw家族Kv3.1和Kv3.3通道以及双孔家族 rTWIK通道在神经元中以高水平表达，这些神经元能够 以非常快的速度放电，并将它们的动作电位锁定在特定的 听觉刺激的阶段。我们计划确定调控机制 这些通道位于耳蜗核神经元的突触前末梢， 它们的突触后靶点，斜方核内侧核的神经元 身体为了测试这些通道在时间和调节的作用， 递质释放，我们将记录神经元终端的反应， 这些通道的基因已经被同源的 重组我们将检验通道的磷酸化 蛋白质改变了通过这种突触途径的信息传递。 使用转基因动物，其中通道的启动子与 荧光报告基因，我们将测试是否自然发生的 Kv3.1通道沿着张力分布区的表达水平的差异 轴可以由神经元活动模式的变化引起， 都暴露了了解离子通道是如何在中枢神经系统中调节的 听觉神经元可能会导致某些形式的耳聋的治疗， 以及耳鸣，听觉刺激解释障碍， 和过度兴奋状态如听源性癫痫发作。

DESCRIPTION: The firing patterns of neurons in central auditory pathways encode specific features of sound stimuli, such as frequency, intensity and localization in space. The generation of the appropriate pattern depends, to a major extent, on the properties of the voltage-dependent potassium channels in these neurons. The Shaw-family Kv3.1 and Kv3.3 channels and the two-pore family rTWIK channel are expressed at high levels in neurons that are capable to firing at very rapid rates and that lock their action potentials to specific phases of auditory stimuli. We plan to determine the mechanisms that regulate these channels in the presynaptic terminals of cochlear nucleus neurons and their postsynaptic targets, neurons of the medial nucleus of the trapezoid body. To test the roles of these channels in timing and regulation of transmitter release, we shall record the responses of neuronal terminals and somata in which the genes for these channels have been eliminated by homologous recombination. We shall test the hypothesis that phosphorylation of the channel proteins alters the transmission of information through this synaptic pathway. Using transgenic animals in which the promoters for the channels are coupled to a fluorescent reporter gene, we shall test whether the naturally occurring differences in the level of expression of the Kv3.l channel along tonotopic axes can be induced by changes in the pattern of activity to which the neurons are exposed. An understanding of how ion channels are regulated in central auditory neurons is likely to lead to therapies for certain forms of deafness, as well as for tinnitus, disorders in the interpretation of auditory stimuli, and states of hyperexcitability such as audiogenic seizures.