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Science 19 January 1996:
Vol. 271. no. 5247, pp. 369 - 373
DOI: 10.1126/science.271.5247.369
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Reports

Zinc-Induced Collapse of Augmented Inhibition by GABA in a Temporal Lobe Epilepsy Model

Eberhard H. Buhl,  Thomas S. Otis,  Istvan Mody (1)

In the kindling model of temporal lobe epilepsy, several physiological indicators of inhibition by -aminobutyric acid (GABA) in the hippocampal dentate gyrus are consistent with an augmented, rather than a diminished, inhibition. In brain slices obtained from epileptic (kindled) rats, the excitatory drive onto inhibitory interneurons was increased and was paralleled by a reduction in the presynaptic autoinhibition of GABA release. This augmented inhibition was sensitive to zinc most likely after a molecular reorganization of GABAA receptor subunits. Consequently, during seizures, inhibition by GABA may be diminished by the zinc released from aberrantly sprouted mossy fiber terminals of granule cells, which are found in many experimental models of epilepsy and in human temporal lobe epilepsy.


E. H. Buhl, MRC Anatomical Neuropharmacology Unit, Oxford University, Mansfield Road, Oxford OX1 3TH, UK.
T. S. Otis, Department of Neurophysiology, University of Wisconsin Medical School, Medical Sciences Center, 1300 University Avenue, Madison, WI 53706-1532, USA.
I. Mody, Department of Neurology RNRC 3-131, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
(1) To whom correspondence should be addressed.


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In Vivo Intracellular Analysis of Granule Cell Axon Reorganization in Epileptic Rats.
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""The seat of the discharge"" and the molecules that govern seizures.
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Temporal Patterns and Depolarizing Actions of Spontaneous GABAA Receptor Activation in Granule Cells of the Early Postnatal Dentate Gyrus.
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J Neurophysiol 80, 2340-2351
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Zinc and Zolpidem Modulate mIPSCs in Rat Neocortical Pyramidal Neurons.
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Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy.
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Slow Kinetics of Miniature IPSCs during Early Postnatal Development in Granule Cells of the Dentate Gyrus.
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Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABAB Receptors.
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Long-term plasticity in interneurons of the dentate gyrus.
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