GABAergic signalling in temporal lobe epilepsy

Earlier studies on temporal lobe epilepsy (TLE), by focusing on the anatomical and electrophysiological abnormalities of the hippocampus, have attributed a major role to this limbic structure in the process of epileptogenesis and seizure generation. Recently however, there has been increasing evidence from both animal and human studies that other limbic structures, including the subiculum, the entorhinal cortex (EC, perirhinal cortex (PC) as well as the amygdala, are possibly involved in the process of epileptogenesis. With the help of both acute and chronic models of limbic seizures, I have used an electrophysiological approach to gain more insight into the mechanisms through which these structures could participate in the establishment of hyperexcitable neuronal networks. Particularly, my investigations have focused on assessing the role played by the subiculum, the amygdala and the PC in epileptiform synchronization in vitro. My findings demonstrate that seizure-induced cell damage in chronically epileptic mice results in a change in limbic network interactions whereby EC ictogenesis is sustained via a reverberant EC-subiculum pathway ( Chapter 1). Furthermore, I have discovered that the subiculum, which holds an anatomically strategic position within the hippocampus, is capable of gating hippocampul output activity via a GABAA-receptor mediated mechanism (Chapter 2). My investigations in the amygdala have confirmed that this limbic structure contributes to epileptiform synchronization (Chapter 3). Moreover, using a chronic rat model of TLE, I have found novel evidence suggesting that alterations in inhibitory mechanisms play a role in the increased excitability of the lateral amygdalar nucleus (Chapter 4). Finally, my studies in chronically epileptic rats have also led to preliminary data signifying hyperexcitability of the PC as well alterations in the interactions between the amygdala and this cortical structure (Chapter 5)