Towards a unified model of action potential generation

 描述(由申请人提供)：轴突初始段具有独特的离子通道组成，使动作电位启动。研究这个隔区的生物物理特性对于了解神经元的兴奋性和相关的神经元疾病，包括癫痫，是至关重要的。最近，我们发现钙通道聚集在起始段。我们的实验室表明，这些通道在神经元兴奋性中起着关键作用，并且这些通道受到多巴胺神经调节的影响。起始段的现代模型包括钠通道和钾通道的真实分布，但不包括钙通道。在这里，我们的目标是利用电生理和成像技术，在急性脑片上 以及异源系统，以了解钙通道在动作电位启动中的作用，并确定多巴胺能信号如何改变轴突钙通道的生物物理特性。这些数据将被纳入使用新的基于GPU的模拟环境的轴突初始段兴奋性的新模型中。

 DESCRIPTION (provided by applicant): The axon initial segment has a unique composition of ion channels that enables action potential initiation. Studying the biophysical properties of this compartment is crucial for understanding neuronal excitability and associated neuronal disorders, including epilepsy. Recently, we found that Ca channels are clustered in the initial segment. Our lab showed that those channels play a critical role in neuronal excitability, and that these channels are subject to dopamine neuromodulation. Modern models of the initial segment includes realistic distributions of Na and K channels, but do not include Ca channels. Here, our goal is to utilize electrophysiological and imaging techniques, both in acute brain slice and heterologous systems, to understand the role of Ca channels in action potential initiation, and to determine how dopaminergic signaling alters the biophysical properties of axonal Ca channels. These data will be incorporated into new models of axon initial segment excitability using novel, GPU-based simulation environments.