Spontaneous excitatory currents and kappa-opioid receptor inhibition in dentate gyrus are increased in the rat pilocarpine model of temporal lobe epilepsy

被引:30
作者
Simmons, ML
Terman, GW
Chavkin, C
机构
[1] UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195
[2] UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98195
关键词
D O I
10.1152/jn.1997.78.4.1860
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Temporal lobe epilepsy is associated with a characteristic pattern of synaptic reorganization in the hippocampal formation, consisting of neuronal loss and aberrant growth of messy 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 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 spontaneous excitatory postsynaptic currents (EPSCs) was increased greatly in cells from tissue in which significant messy fiber sprouting had developed. In the presence of bicuculline, giant spontaneous EPSCs, with large amplitudes and long durations, were seen only in association 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 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 messy 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.
引用
收藏
页码:1860 / 1868
页数:9
相关论文
共 44 条