Thesis (Ph. D.)--University of Virginia, 2000.
Spine title: Disruption of inhibition in epilepsy. Includes bibliographical references (p. 186-207). Also available online through Digital Dissertations.
Mesial temporal lobe epilepsy (TLE) is a syndrome of reoccurring seizures that generate within the limbic system. The hippocampus, a brain structure associated with learning and memory tends to be ...one of the primary foci for seizure generation. This project sought to establish if a loss of a particular population of neurons in the entorhinal cortex (EC) would cause disruption of inhibition to its target neurons in the hippocampus. Since the hippocampus receives substantial projections from the EC and a loss of layer III neurons in the EC has been described in patients with TLE (Du et al., 1993), the loss of the projection from layer III neurons may be an important component in the generation of seizures. Using an animal model where the indirect excitotoxin, aminooxyacetic acid (AOAA) was injected directly into the EC, we could preferentially kill the layer III neurons of the EC. Through evoked potentials and paired pulse inhibition, we assessed the functional effects of this cell loss on different regions of the hippocampus and looked at the time course of this damage. We also determined that the loss of inhibition was specific to area CA1 of the hippocampus and not evident following complete ablation of the EC, while the ablation of the AOAA-injected only attenuated some of the hyperexcitable responses from CA1. The interneuron population within CA1 was examined in order evaluate if the loss of inhibition was caused by a selective loss of inhibitory neurons. Finally, the seizure susceptibility of the hippocampus was appraised in this AOAA model. Therefore, in this animal model of epilepsy, we evaluated whether the loss of a select group of neurons within layer III of the EC affect the inhibitory efficacy of the pyramidal cell layer in CA1 or whether the preliminary seizures caused by AOAA are responsible for disrupted inhibition within CA1. The loss of layer III neurons in the EC may not be a model of seizure generation itself, but it may be one of several components critical for the induction of seizures.
