SPONTANEOUS EXCITATORY CURRENTS AND KAPPA-OPIOID RECEPTOR INHIBITION IN DENTATE GYRUS ARE INCREASED IN THE RAT PILOCARPINE MODEL OF TEMPORAL-LOBE EPILEPSY

Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of ne uronal loss and aberrant growth of messy fiber collaterals into the de ntate gyrus inner molecular layer. We have used the rat pilocarpine mo del of temporal lobe epilepsy to study the functional consequences of messy 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 s pontaneous excitatory postsynaptic currents (EPSCs) was increased grea tly in cells from tissue in which significant messy fiber sprouting ha d developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in associatio n with messy fiber sprouting. Giant EPSCs also could be evoked by low- intensity stimulation of the perforant path. Messy fibers release not only excitatory amino acids, but also opioid peptides. kappa-Opioid re ceptor-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 vent ral and more dorsal sections. Thus in this model of temporal lobe epil epsy, several types of abnormal excitatory activity were observed, the reby supporting the idea that messy fiber sprouting leads to recurrent excitatory connections. At the same time, inhibition of excitatory ac tivity by kappa-opioid receptors was increased, perhaps representing a n endogenous anticonvulsant mechanism.