Development of two in vitro methodologies for the study of brain network dynamics and an application to the study of seizure-evoked adenosine release

Abstract

Understanding the brain in both health and disease is of critical practical importance as well as fundamental scientific interest. The acute neural tissue slice is a widely used experimental preparation, it facilitates treatments and measurements not practical in vivo while preserving a largely connected network representative of the true in vivo structure. This thesis presents the development of two techniques for the study of the acute neural tissue slice, both particularly well suited to the study of epilepsy, followed by an application of one of these techniques. A slice chamber is presented that allows extended regions of a tissue slice to be exposed, in isolation, to changes in ionic environment or pharmacological manipulation, readily providing an entirely in vitro model of focal epilepsy. Secondly, a transformation is derived that converts the slow dynamics of the intrinsic optical signal (IOS) associated with neuronal activity both in vivo and in vitro to the form of the associated local field potential, allowing the advantages of the IOS to be exploited while mitigating the primary disadvantage - the lack of direct correspondence between the IOS and the associated network dynamics. Finally a study is presented that employs the transformation of the IOS to facilitate a quantitative characterisation of the spatio-temporal dynamics of adenosine release in response to electrographic seizure activity