Alterations in GABAA receptor expression and physiology in a mouse model of idiopathic generalized epilepsy

Abstract

The proper function of the nervous system is dependent upon a delicate balance between excitatory and inhibitory activity in the brain. GABAA receptors are extremely important in the maintenance of this balance because they mediate the majority of fast inhibition in the adult central nervous system. Several genetic mutations in various human GABAA receptor subunits have been associated with idiopathic generalized epilepsy syndromes. Here we have investigated the consequences of GABAA receptor dysfunction using a mouse model based on one of the aforementioned genetic mutations identified in a human epilepsy patient. We begin with a general introduction to epilepsy followed by a more detailed discussion of the particular epilepsy syndrome studied herein. We then provide a thorough review of GABAA receptor structure and function and highlight previous findings related to our current studies. We then provide an explanation of the rationale and general experimental strategy employed in our studies. Next we provide the specifics of our methodology proceeded by the presentation of our results. In the final chapter we discuss our interpretation of the data and its implications for the advancement of our understanding of epilepsy.