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，大脑的许多方面 诸如强度、音调和定位之类的刺激在很大程度上被编码 通过听觉回路中神经元的暂时性放电模式。这个 神经元放电的时间和速度在很大程度上取决于 以及它所拥有的离子电导的数量。特别是，最近的研究 都强调了电压依赖性钾通道在形成中的作用 不同脑干听觉神经元对声音刺激的反应。 现在已经分离出大量K+通道的基因，并且 通过在非洲爪哇表达研究它们的电生理特性 卵母细胞和不可兴奋的细胞系。我们已经在现场确认了 杂交和免疫组织化学，一种K+通道，The Show KV3.1，特别丰富了听觉的子集的频道 神经元。这些KV3.1通道与电流之间的关系 在真实的听觉神经元中被记录下来，目前还没有确定。 然而，我们正在进行的建模研究表明，这些渠道 对于保存快速突触输入的时间可能很重要。这个 本提案的目标是建立KV3.1渠道的功能角色 在听觉神经元中。EM免疫组织化学方法将用于检测 KV3.1通道在听神经元中的准确亚细胞分布，以及 具有不同突触模式的神经元是否也是如此 输入。此外，还将使用免疫学技术来识别 其他可能与KV3.1蛋白异构化的K+通道亚基。 要确定KV3.1通道对外向电流的贡献 听觉神经元、电生理测量将对 严格比较听觉神经元的电流和KV3.1电流 在细胞系中单独表达或与其他K+通道亚基一起表达。这 还将在以下情况下进行比较： 选择性地改变表达以进一步验证KV3.1组件。 最后，混合阻止技术和/或基因敲除将被用于 直接评估KV3.1通道在调节时间方面的参与 单个听觉神经元的动作电位。这些研究应该 提供有关确定 某些听觉神经元的特征放电模式，并可能推进 对加工过程中涉及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.