Role of EAG K+ Channels in Cortical Function

动作电位是整个动物界神经系统的普遍信号。动作电位在神经系统的不同部分和不同动物之间非常相似。信息被编码在一系列动作电位的频率和时间模式中。有几个因素促成了这些模式的产生。其中，携带钾离子（K+）离子通道的多样性，被称为K+通道，是影响神经信号形成的主要因素之一。近年来，通过遗传分子分析发现了大量新的K+通道。随着几种动物基因组的完整序列的公布，预计还会有更多的发现。未来研究的一个主要任务是了解这些通道的生理作用。该项目将研究一个新的K+通道基因家族，称为EAG，最近从苍蝇和哺乳动物中发现并克隆。EAG基因的产物已被引入模型细胞，在那里它们导致形成具有独特和有趣功能特性的K+通道。这项任务是确定它们在大脑的原生环境中是否具有相同的特性，并揭示它们在神经信号传导中的作用。为了发现EAG通道的功能作用，实验旨在探索哪些脑细胞通常含有编码这些通道的基因的产物。然后使用电生理技术来研究它们在天然细胞中的特性，以及它们在形成神经元信号中的作用。申请人实验室之前的研究表明，一些EAG基因产物在大脑皮层的神经元中特别突出，它们独特的分布表明EAG通道在特定的皮层回路中起着特定的作用。该项目将测试eeg通道在调节特定皮层神经元的兴奋性状态方面具有关键功能的假设，包括决定感觉信息是否进入大脑皮层，从而调节意识状态。这项研究将有助于揭示新的K+通道基因的功能，并促进我们对大脑处理信息的机制的理解。这项研究将有助于发现新发现基因作用的方法的发展，以及对研究生的多学科培训。

The action potential is the universal signal in the nervous system throughout the animal kingdom. Action potentials are very similar in different parts of the nervous system and between different animals. Information is instead encoded in the frequency and temporal pattern of series of action potentials. Several factors contribute to generating these patterns. Among these, the diversity of ion channels carrying, potassium (K+) ions, known as K+ channels, is one of the main factors contributing to the shaping of neural signals. A large number of new K+ channels have been discovered recently through genetic molecular analysis. Additional discoveries can be expected as the full sequence of the genomes of several animals becomes known. A major task of future research is to understand the physiological roles of these channels. This project will study a new K+ channel gene family, known as EAG, recently identified and cloned from flies and mammals. The products of EAG genes have been introduced into model cells, where they result in the formation of K+ channels with unique and intriguing functional properties. The task is to determine if they have the same properties in their native environment in the brain and to unravel their roles in neural signaling. To discover the functional roles of EAG channels, experiments are designed to explore which brain cells normally contain the products of the genes encoding these channels. Electrophysiological techniques are then used to study their properties in native cells, and their role in shaping neuronal signals. Previous investigations in the applicant's laboratory have shown that several EAG gene products are particularly prominent in neurons in the cerebral cortex, and their unique distributions suggest that EAG channels play specific roles in particular cortical circuits. This project will test the hypothesis that EAG channels have crucial functions in regulating the state of excitability of specific cortical neurons, including determining whether or not sensory information enters the cerebral cortex and hence in modulating states of consciousness. This study will contribute to the unraveling of the function of novel K+ channel genes and advance our understanding of the mechanisms by which the brain processes information. This study will contribute to the development of methods to discover the roles of newly found genes, and multidisciplinary training to a graduate student.