Effect of low frequency stimulation of perforant path on kindling acquisition and synaptic transmission in the dentate gyrus in rats

Introduction: Previous studies have shown that low frequency stimulation (LFS) has an inhibitory effect on kindling acquisition. However, the mechanism of this effect has not been completely determined. In the present study, the effect of LFS of the perforant path on seizures induced by rapid perforant path kindling was investigated. Methods: Animals were kindled by electrical stimulation of perforant path. One group of animals (n=6) received LFS (0.1 ms pulses at 1 Hz, 200 pulse, and 50-150 μA) after termination of each kindling stimulations. In control groups, animals received only kindling stimulations (n=8) or LFS (n=4). Basal field potential recording and paired pulse stimulations were done every day, before kindling stimulations. Results: Application of LFS significantly retarded the kindling acquisition and increased the number of stimulations to achieve different seizure stages [F(4,60)=10.9, P<0.0001]. LFS also prevented increment of slope of field excitatory postsynaptic potentials and population spike amplitude during kindling (P<0.001) (There was 88.6±1.7% increment in fEPSP and 94±2.3% increment in PS in kindled group and 3.5±.05% increment in fEPSP and 12.3±0.1% decrease in PS in kindled+LFS group). In addition, LFS significantly prevented the marked increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression induced by kindling (P<0.01). Conclusion: According to obtained results, it may be suggested that LFS of perforant path has a significant antiepileptogenic effect on perforant path kindled seizures through inhibition of synaptic transmission in dentate gyrus. Meanwhile, LFS prevents compensatory increase in the paired pulse depression during kindling acquisition.