Spontaneous Excitatory Currents and Kappa Opioid Receptor Inhibition in Dentate Gyrus are Increased in the Rat Pilocarpine Model of Temporal Lobe Epilepsy. Michele L. Simmons, Gregory W. Terman and Charles Chavkin. Departments of Pharmacology and Anesthesiology, University of Washington, Seattle, WA 98195-7280.
APStracts 4:0116N, 1997.
ABSTRACT
Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of mossy fiber collaterals into the dentate gyrus inner molecular layer. We have used the rat pilocarpine model of temporal lobe epilepsy to study the functional consequences of mossy fiber sprouting on excitatory activity and kappa opioid receptor-mediated inhibition. Using the whole cell voltage clamp technique, we found that abnormal excitatory activity was evident in granule cells of the dentate gyrus from pilocarpine-treated rats. The frequency of spontaneous EPSCs was greatly increased in cells from tissue in which significant mossy fiber sprouting had developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in association with mossy fiber sprouting. Giant EPSCs also could be evoked by low intensity stimulation of the perforant path. Mossy fibers release not only excitatory amino acids, but also opioid peptides. Kappa opioid receptor-mediated inhibition in normal Sprague-Dawley rats was seen only in hippocampal sections from the ventral pole. In pilocarpine-treated rats, however, kappa receptor-mediated effects were seen in both ventral and more dorsal sections. Thus, in this model of temporal lobe epilepsy, several types of abnormal excitatory activity were observed, thereby supporting the idea that mossy fiber sprouting leads to recurrent excitatory connections. At the same time, inhibition of excitatory activity by kappa opioid receptors was increased, perhaps representing an endogenous anticonvulsant mechanism. 

Received 11 June 1997; accepted in final form 25 June 1997.
APS Manuscript Number J239-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 July 1997