Abstracts

How GABA-mediated inhibition is altered after a brain insult (e.g., status epilepticus), and the role of inhibition during epileptogenesis remain unclear. The present study aimed to examine short- and long-term (i.e., 4-7 days vs. [gt]3 months) changes of inhibition in dentate granule cells after kainate-induced status epilepticus. Previous data with this model has revealed that these rats develop spontaneous seizures, and have hilar neuron loss with robust mossy fiber sprouting.
Hippocampal slices were prepared from Sprague-Dawley rats 4-7 days or [gt]3 months after kainate or saline treatment. Whole-cell patch-clamp techniques were used to record spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) of dentate granule cells. The sIPSCs were obtained with CsCl-containing pipets and the holding potential at -70 mV in DNQX (50 [mu]M) and AP-5 (50 [mu]M). The mIPSCs were obtained by adding TTX (2 [mu]M) to the medium. Bicuculline (30 [mu]M) was routinely added at the end of each experiment to verify the recorded currents were mediated by GABAA receptors. Most animals were coded so the experimenter was blind to the treatment.
Most recorded neurons (n=73) showed relatively high frequency and large amplitude sIPSCs. Application of TTX eliminated all large-amplitude IPSCs and revealed mIPSCs. In both short- and long-term groups, the mean sIPSC frequency of the saline- and kainate-treated rats was not significantly different. However, mIPSC frequency from the kainate-treated rats of the short-term group was about 30% lower than that of saline controls (p[lt]0.05). The long-term epileptic animals also had significantly fewer mIPSCs than control animals ([sim]30%, p[lt]0.05) (Dudek and Shao, 2002). In contrast, the mean amplitude of the sIPSC or mIPSC was not reduced in kainate-treated rats from both short- and long-term groups.
Our results are consistent with a recent study using pilocarpine model (Kobayashi and Buckmaster, J. Neurosci., 2003. 23:2240-52). Our data on sIPSCs are also consistent with other experiments, particularly in vivo recordings, which have shown robust or even enhanced inhibition in the dentate gyrus in rats with chronic recurrent seizures after status epilepticus. The reduction of mIPSCs frequency (i.e., [sim]30%) shortly after kainate treatment suggests that the status epilepticus caused a partial loss of the inhibitory interneuron population that innervates granule cells. A similar reduction ([sim]30%) of mIPSCs in the long-term kainate group further suggests that the interneuron damage remained unchanged during epileptogenesis.
[Supported by: NS 16683]