Effects of Low Frequency Stimulation on Spontaneous Inhibitory and Excitatory Post-Synaptic Currents in Hippocampal CA1 Pyramidal Cells of Kindled Rats

Abstract

Objective Low-frequency stimulation (LFS) exerts suppressive effects in kindled animals. It is believed that overstimulated glutamatergic and decreased GABAergic transmission have long been associated with seizure activity. In this study, we investigated the effect of electrical LFS on different parameters of spontaneous excitatory and inhibitory post-synaptic currents (sEPSCs and sIPSCs) in hippocampal CA1 pyramidal cells in kindled animals. Materials and Methods In this experimental study, rats were kindled by electrical stimulation of the hippocampal CA1 area in a semi-rapid manner (12 stimulations/day). The animals were considered fully kindled when they showed stage 5 seizures on three consecutive days. One group of animals received LFS 4 times at 30 seconds, 6 hours, 18 and 24 hours following the last kindling stimulation. Each LFS consisted of 4 packages at 5 minutes intervals. Each package of LFS consisted of 200 pulses at 1 Hz and each monophasic square wave pulse duration was 0.1 millisecond. At 2-3 hours post-LFS, acute hippocampal slices were prepared and a whole cell patch clamp recording was performed in all animals to measure the different parameters of sEPSCs and sIPSCs. Results In kindled animals, the inter-event interval (as an index of occurrence) of sEPSCs decreased, whereas sIPSC increased. In addition, the decay time constant of sIPSCs as an index of the duration of its activity decreased compared to the control group. There was no significant difference in other parameters between the kindled and control groups. Application of LFS in kindled animals prevented the observed changes. There was no significant difference between the measured parameters in kindled+LFS and control groups. Conclusion LFS application may prevent seizure-induced increase in the occurrence of sEPSCs and seizure-induced decrease in occurrence and activity duration of sIPSCs.