Expression of Ion Channels in the Auditory System

描述：中枢听觉通路神经元的放电模式编码 声音刺激的特定特征，如频率、强度和 太空中的本地化。适当图案的生成取决于 在很大程度上，对电压依赖性钾通道的性质 这些神经元。Shaw家族Kv3.1和Kv3.3通道和两孔家族 RTWIK通道在神经元中高水平表达，能够 以非常快的速度发射，将它们的动作电位锁定在特定的 听觉刺激的不同阶段。我们计划确定监管的机制 这些通道位于耳蜗核神经元突触前终末和 它们的突触后靶，即梯形体内核的神经元 尸体。测试这些渠道在计时和调节中的作用 释放递质时，我们将记录神经元终末的反应和 这些通道的基因已被同源基因消除的体细胞 重组。我们将测试通道的磷酸化的假设 蛋白质通过这种突触途径改变信息的传递。 使用转基因动物，其中通道的启动子连接到 一种荧光报告基因，我们将测试自然发生的 正位Kv3.1通道表达水平的差异 轴可以通过改变神经元的活动模式来诱导 都被暴露了。对中枢神经系统离子通道如何调节的理解 听觉神经元可能会导致某些形式的耳聋的治疗， 以及耳鸣，听觉刺激解释方面的障碍， 以及过度兴奋状态，如听源性癫痫。

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.