Chloride regulation in neuronal development and epilepsy

神经系统的特点是高度组织的“回路”，其中特定的神经细胞群或神经元相互连接。神经元的交流方式取决于它们的三维结构和它们彼此之间形成的连接类型。神经回路是在发育过程中形成的，这些早期阶段的错误可能会导致以后的问题。例如，癫痫和精神分裂症只是两种疾病，其中异常的发育事件被认为是成人大脑异常交流的基础。这项研究的重点是氯离子，这是神经系统中的一种关键离子。已经观察到，在神经回路发育期间，神经元内氯离子的水平通常会下降。相反，癫痫患者大脑中的神经元含有异常高水平的氯化物。利用啮齿类动物的神经组织，这个项目中的实验将研究氯水平的变化如何影响生长中的神经元的结构和连接。此外，它将解决在发育过程中控制氯化物水平的分子本身是如何被调节的。这项工作的发现将促进我们对新生儿发育的理解，以及我们对神经系统常见疾病中发生的细胞变化的理解。

The nervous system is characterised by highly organised ‘circuits’ in which specific groups of nerve cells, or neurons, interconnect. The way neurons communicate depends upon their three dimensional structure and the type of connections that they form with one another. Neural circuits are laid down during development and errors at these early stages can lead to problems later in life. For instance, epilepsy and schizophrenia are just two disorders where abnormal developmental events are thought to underlie aberrant communication in the adult brain.This research focuses upon chloride, a key ion in the nervous system. It has been observed that the level of chloride inside neurons normally decreases during the period that neural circuits are developing. In contrast, neurons in the brains of epilepsy patients have abnormally high levels of chloride. Using neural tissue from rodents, the experiments in this project will examine how changes in chloride levels influence the structure and connections of growing neurons. Furthermore, it will address how molecules that control chloride levels are themselves regulated during development.Findings from this work will advance our understanding of neonatal development, and also our understanding of the cellular changes that occur in common disorders of the nervous system.