Abstracts

Rationale: Status epilepticus is a neurological emergency characterized by a prolonged, self-sustained seizure. Rapid modifications of GABAergic and glutamatergic synaptic transmission during this dynamic, evolving syndrome are, in part, the result of rapid activity-dependent changes in the surface expression of the GABAergic and glutamatergic postsynaptic receptor pools. This study was undertaken to better define the changes in synaptic transmission at not only the principal neurons but also interneurons within the dentate gyrus network.Methods: Status epilepticus was induced in postnatal day 13 to 25 Sprague-Dawley rats using lithium/pilocarpine (SE-treated). Whole cell patch clamp recordings were obtained from morphologically-identified basket cells (interneurons) located within the dentate gyrus and dentate granule cells (DGCs) in acutely obtained hippocampal slices from SE-treated animals and na ve age-matched controls. The SE-treated animals were euthanized one hour after the first Racine stage 5 seizure. 8 to 11 cells were recorded in each condition for each group.Results: Miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory postsynaptic currents (mEPSCs) recorded from DGCs in SE-treated slices were distinct from those recorded from controls: mIPSC amplitude was reduced by 45%, mIPSC frequency was reduced by 60%, mEPSC amplitude was increased by 45%, and mEPSC frequency was increased by 200%. In contrast, the mIPSCs recorded from SE-treated interneurons were similar in amplitude as well as frequency, rise-time and weighted decay. Furthermore, the frequency and amplitudes of spontaneous inhibitory currents (sIPSC) recorded from SE-treated interneurons were similar to controls. The frequency of mEPSCs and spontaneous excitatory currents (sEPSC) recorded from the SE-treated interneurons was increased (69% and 50%, respectively) compared to controls. Despite this increase in the frequency of excitatory inputs to the interneurons, the frequency and amplitude of sIPSCs recorded from DGCs were reduced (42% and 49%, respectively) whereas the frequency and amplitude of sEPSCs were increased (23% and 56%, respectively).Conclusions: These findings confirm prior findings of a decrease in GABA-mediated inhibition and increase in glutamatergic excitation of DGCs as the result of status epilepticus. The decrease in GABA-mediated inhibition is not widespread but cell-specific as GABA-mediated inhibition of the population of interneurons was not diminished. A novel finding was the demonstration that an increase in the excitatory barrage of the interneurons did not result in a concomitant increase in the sIPSC frequency in recordings of DGCs. The net effect of these changes is a shift in the excitatory:inhibitory balance that favors a hyperexcitable network during status epilepticus.