Prolonged GABA Responses In Dentate Granule Cells In Slices Isolated From Patients With Temporal Lobe Sclerosis. Williamson, Anne, Albert E. Telfeian and Dennis D. Spencer. Sections of Neurosurgery and Neurobiology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520 and Department of Neurological Surgery, University of Pennsylvania School of Medicine.
APStracts 2:0113N, 1995.
SUMMARY AND CONCLUSIONS
1. Medial temporal lobe sclerosis is a common pathological finding in patients with medically intractable temporal lobe epilepsy. This disease is characterized by extensive cell loss in the hilus, and the hippocampal CA1 and CA3 cell fields in addition to synaptic reorganization throughout the dentate gyrus. 2. The dentate granule cells from slices of hippocampi of patients diagnosed with medial temporal lobe sclerosis exhibit reduced synaptic inhibition with concommitant hyperexcitability. These physiological changes were studied relative to the hippocampi of patients with temporal lobe tumors in which the cell loss and synaptic reorganization are not seen. 3. We attempted to determine if this disinhibition was due to changes in the post- synaptic sensitivity to the inhibitory neurotransmitter g-aminobutyric acid (GABA) by studying the responses to exogenously applied transmitter. As in rodents, the GABA responses in human dentate granule cells studied at the resting membrane potential were depolarizing and were mediated primarily by GABAA receptors. In many cases, these depolarizing GABA responses could trigger action potentials. Thus, in some situations, GABA could act as an excitatory neurotransmitter. 4. We found that GABAA receptor-mediated responses in the sclerotic hippocampi were approximately 80% longer than in the comparison population. This difference was not due to changes in either the GABA reversal potential or the GABA-induced conductance change. The data support the hypothesis that the GABA transport system is impaired in sclerotic tissue: application of the GABA uptake inhibitor NNC711 (a tiagibine derivitive) greatly prolonged the GABA responses in the TTLE tissue, but had little effect on the sclerotic tissue. 

Received 6 June 1994; accepted in final form 20 March 1995.
APS Manuscript Number J320-4.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  1 May 1995.