POTASSIUM CHANNELS IN AUDITORY TEMPORAL PROCESSING

虽然一些关于听觉刺激的信息，如声音频率， 由活跃神经元的空间模式编码， 诸如强度、音高和定位的刺激在很大程度上被编码 听觉回路中神经元的时间放电模式。 的 神经元放电的时间和速率很大程度上取决于 和它所具有的离子电导的量。 特别是，最近的研究 已经强调了电压依赖性钾通道在塑造 不同脑干听觉神经元对声音刺激的反应。 大量K+通道的基因现在已经被分离出来， 通过在非洲爪蟾中表达研究其电生理特性 卵母细胞和非兴奋细胞系。 我们已经通过现场鉴定 杂交和免疫组织化学，一种类型的K+通道，显示 Kv3.1，通道，特别是在听觉的子集丰富， 神经元 这些Kv3.1通道与电流的关系， 在真实的听觉神经元中的记录尚未建立。 然而，我们正在进行的建模研究表明，这些通道 对于保持快速突触输入的定时可能是重要的。 的 本提案的目标是确定Kv3.1通道的功能作用 在听觉神经元中。 EM免疫组化将用于检查 Kv3.1通道在听觉神经元中的确切亚细胞分布，以及 对于具有不同突触模式的神经元， 输入. 此外，免疫学技术将用于识别 其他可能与Kv3.1蛋白异源同源的K+通道亚基。 为了确定Kv3.1通道对外向电流的贡献， 听觉神经元，将进行电生理测量， 将听觉神经元中的电流与Kv3.1电流进行严格比较 在细胞系中单独或与其它K+通道亚基一起表达。 这 还将在Kv3.1水平的情况下进行比较， 选择性地改变表达以进一步验证Kv3.1组分。 最后，杂交抑制技术和/或基因敲除将用于 直接评估kv3.1通道参与调节时间 听觉神经元的动作电位。 这些研究应 提供资料，说明在确定 某些听觉神经元的特征性放电模式， 对参与处理的潜在生理学的理解， 快速听觉信息

Although some information about auditory stimuli such as sound frequency is encoded by the spatial pattern of active neurons, many aspects of the stimulus such as the intensity, pitch and localization are largely encoded by the temporal discharge patterns of neurons in auditory circuits. The timing and rate at which a neuron fires is largely determined by the types and amounts ionic conductances it possesses. In particular, recent studies have emphasized the role of voltage-dependent potassium channels in shaping the responses of different brainstem auditory neurons to a sound stimulus. The genes for a large number of K+ channels have now been isolated, and their electrophysiological properties investigated by expression in Xenopus oocytes and non-excitable cell lines. We have identified by in situ hybridization and immunohistochemistry, one type of K+ channel, the Show Kv3.1, channel which is particularly enriched in a subset of auditory neurons. The relationship of these Kv3.1 channels to the currents that have been recorded in real auditory neurons has not been established. However, our ongoing modeling studies have suggested that these channels may be important for preserving the timing of rapid synaptic inputs. The goal of this proposal is to establish the functional role of Kv3.1 channels in auditory neurons. EM immunohistochemistry will be used to examine the exact subcellular distribution of Kv3.1 channels in auditory neurons, and whether this is the same for neurons with differing patterns of synaptic input. In addition, immunological techniques will be used to identify other K+ channel subunits which may heteroligermize with Kv3.1 proteins. To determine the contribution of the Kv3.1 channel to outward currents of auditory neurons, electrophysiological measurements will be made to rigorously compare currents in auditory neurons with Kv3.1 currents expressed alone or with other K+ channel subunits in cell lines. This comparison will also be made in situations where the level of Kv3.1 expression is selectively altered to further verify the Kv3.1 components. Finally, hybrid arrest techniques and/or gene knockout will be used to directly assess the involvement of kv3.1 channels in regulating the timing of action potentials in individual auditory neurons. These studies should provide information on the mechanisms involved in determining the characterized firing patterns of certain auditory neurons and may advance the understanding of the underlying physiology involved in processing of rapid auditory information.