Chloride regulation in neuronal development and epilepsy

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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.