Date of Graduation
School of Medicine
Physiology, Pharmacology & Neuroscience
David A. Taylor.
The genetically epilepsy-prone rat (GEPR) is an animal model of epilepsy which exhibits deficits in GABAergic neurotransmission in a variety of brain regions. However, the underlying cause for this deficit has yet to be described. The present studies were therefore performed in order to elucidate the mechanism(s) underlying this GABAergic deficit. To accomplish this task, electrophysiological recordings of Purkinje neurons in sagittal slices of the cerebellar vermis were performed. The initial aim was to compare the basic electrical membrane characteristics of Purkinje neurons from GEPR and control animals using standard intracellular recording techniques. These studies indicated that there is no significant difference in resting membrane potential or input resistance between GEPRs and control. To compare GEPR and control neurons pharmacologically, full concentration response curves were constructed for membrane polarization responses to GABA, muscimol, glutamate, and aspartate. While there was an approximate 4-fold increase in the GABA and muscimol EC50s for GEPR Purkinje neurons compared to control animals without a change in maximal response, EC50s generated for glutamate and aspartate were not significantly different between animal strains, indicating a specific subsensitivity to GABAA-receptor activation for GEPR Purkinje neurons. In order to further investigate the underlying cause of this specific subsensitivity, whole and single-channel patch recording techniques were used to compare conductance properties of GABAA-receptors from Purkinje neurons from GEPR and control animals. These studies indicated that GEPR Purkinje neuron GABA A-receptors display a decreased level of maximal chloride conductance upon activation by ligand as well an increased rate of desensitization. This provides further evidence that GEPR Purkinje neurons display a specific subsensitivity to GABAA-receptor activation which is due to the chloride gating characteristics of this receptor complex.
Molnar, Lance Russell, "Cellular mechanisms of altered neuronal sensitivity in the genetically epilepsy-prone rat" (1998). Graduate Theses, Dissertations, and Problem Reports. 3150.