Mechanisms of zinc-sensitive metal-regulatory transcription factor 1 induction of hippocampal epileptic network activity (C03)

本项目将重点研究在颞叶癫痫中出现过度兴奋的海马区网络的潜在机制。该项目表明，金属调节转录因子1(MTF1)通过上调CaV3.2钙通道，在驱动海马神经元子集向爆发性行为转变过程中起关键作用。该项目将使用分子、生化和电生理方法的组合来确定癫痫网络活动中对锌敏感的MTF1反应神经元的特征。它将开发一个显示MTF-1活性的神经元的遗传标签，然后分析这一细胞子集与电路的整合。体外和体内的生理学和成像将被用来确定这些细胞如何在癫痫网络中进行功能整合。

This project will focus on the mechanisms underlying the emergence of a hyperexcitable hippocampal network in temporal lobe epilepsy. The project has shown that a metal-regulatory transcription factor 1 (MTF1) is crucial in driving transformation of a subset of hippocampal neurons to bursting behavior via up-regulation of the CaV3.2 calcium channel. The project will use a combination of molecular, biochemical and electrophysiological approaches to determine the characteristics of Zn2+-sensitive MTF1-responsive neurons in epileptic network activity. It will develop a genetic label of neurons exhibiting MTF-1 activity, and then analyze the integration of this subset of cells into the circuit. In-vitro and in-vivo physiology and imaging will be used to determine how these cells are functionally integrated in epileptic networks.