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

高频放电是听觉脑干回路中信号处理的中心特征，参与声源定位。听觉脑干的神经元通过表达专门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双孔钾通道（K2P通道）提供的严格调节的兴奋性。我们和其他人以前的研究发现，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，特别是在听力开始的关键时期，即高频放电模式建立的时候。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，我们将使用最先进的病毒介导的基因转移，从遗传上改变耳蜗腹侧核和听觉脑干斜方体内侧核中K2P通道亚基的表达水平，这是该电路的中央中继站。将通过切片电生理学评估这些遗传修饰对神经元兴奋性和高频放电的影响。我们希望在这个项目中获得的结果将启发这两个特定的K2P通道亚基在神经元兴奋性的调节，从而在听觉处理和声源定位在中央听觉中继的作用。

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.