In vitro studies are invaluable as a primary tool for investigating the cellular and sub-cellular changes implicated in CNS disorders. Whilst many biological experiments use primary cultures, it is difficult to gain control over the parameters that influence the cellular microenvironment and interaction. As a consequence, it is often impossible to decouple and simplify the mechanisms underlying cellular activity, obtaining only averaged responses observed on global cell populations allied to low-throughput and time consuming studies. A viable solution to these problems lies in the use of in vitro miniaturised procedures which enable the formation of simplified structured neuronal networks thus allowing the controlled, localised application of compounds or the localised transfection of cell populations to identify the consequence on cell activity and communication. The aim of this project is to develop novel and high-throughput microfluidic systems for advanced patterning of neuronal cultures that will allow simultaneous optical and electrical recording of cellular activity, as well as enabling CNS drug discovery studies to be conducted using small amounts of novel compounds and the investigation of the consequence on cellular activity of altered protein expression (achieved by knock-down/overexpression) proposed to underlie certain CNS disorders. Finally, combining this system with novel patterning of neuronal cultures will enable the examination of localised neurotoxicity and how it spreads to affect neighbouring microfluidically isolated cultures. Taken together, this project will develop a novel microfluidic platform ideal for in vitro neurobiological studies.