Investigation of the effects of two-pore potassium channels on high frequency signal transmission in the auditory brainstem.

研究双孔钾通道对听觉脑干高频信号传输的影响。

• 批准号: 279586287
• 负责人: Dr. Christoph Körber
• 金额: --
• 依托单位: Institut für Anatomie und Zellbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279586287?language=en
• 关键词: Investigation; effects; two; pore; potassium

High frequency firing is a central characteristic of signal processing in the auditory brainstem circuitry involved in sound source localization. Neurons of the auditory brainstem have adapted to this requirement by expressing specialized sets of voltage-gated ion channels. These channels allow extremely precise high frequency firing, and thereby high fidelity signal transmission, as they constitute very narrow action potentials. However, another prerequisite for high frequency firing of neurons is a tightly regulated excitability, provided by two-pore-potassium channels (K2P channels). Previous studies from us and others found two K2P channel subunits prominently regulated during the postnatal development of the auditory brainstem, particularly in the critical period around the onset of hearing when high frequency firing patterns are established. The proposed project aims at elucidating the roles of these two K2P channel subunits, TREK1 and TASK5, in the regulation of neuronal excitability and subsequently ultra-precisely timed high frequency firing. Therefore, we will genetically alter the expression levels of both K2P channel subunits in the ventral cochlear nucleus and the medial nucleus of the trapezoid body of the auditory brainstem, a central relay station of this circuitry, using state-of-the-art virus-mediated gene transfer. The impact of these genetic modifications on neuronal excitability and high frequency firing will be assessed by slice electrophysiology. We expect that the results obtained in this project will enlighten the roles of these two particular K2P channel subunits in the regulation of neuronal excitability and thereby in auditory processing and sound source localization at a central auditory relay.

高频放电是参与声源定位的听觉脑干电路信号处理的中心特征。听觉脑干的神经元通过表达特殊的电压门控离子通道来适应这一要求。这些通道允许极其精确的高频发射，从而实现高保真信号传输，因为它们构成非常窄的动作电位。然而，神经元高频放电的另一个先决条件是由两孔钾通道（K2P通道）提供的严格调节的兴奋性。我们和其他人之前的研究发现，两个K2P通道亚基在听觉脑干的出生后发育过程中受到显著调节，特别是在听力开始前后的关键时期，此时高频放电模式已经建立。该项目旨在阐明这两个K2P通道亚基TREK1和TASK5在调节神经元兴奋性和随后的超精确定时高频放电中的作用。因此，我们将利用最先进的病毒介导的基因转移，从基因上改变耳蜗前核和听觉脑干梯形体内侧核中K2P通道亚基的表达水平，听觉脑干是该电路的中央中继站。这些基因修饰对神经元兴奋性和高频放电的影响将通过切片电生理学来评估。我们期望本项目获得的结果将揭示这两个特殊的K2P通道亚基在神经元兴奋性调节中的作用，从而在中央听觉中继的听觉加工和声源定位中发挥作用。