ABSTRACT
Objective: Electrical low frequency stimulation [LFS] is a new therapeutic method that moderates hyperexcitability during epileptic states. Seizure occurrence is accompanied by some changes in action potential [AP] features. In this study, we investigated the inhibitory action of LFS on epileptiform activity [EA] induced-changes in AP features in hippocampal CA1 pyramidal neurons
Materials and Methods: In this experimental study, we induced EA in hippocampal slices by increasing the extracellular potassium [K+] concentration to 12 mM. LFS [1 Hz] was applied to the Schaffer collaterals at different pulse numbers [600 and 900] at the beginning of the EA. Changes in AP features recorded by whole-cell patch clamp recording were compared using phase plot analysis
Results: Induction of EA depolarized membrane potential, decreased peak amplitude, as well as the maximum rise and decay slopes of APs. Administration of 1 Hz LFS at the beginning of EA prevented the above mentioned changes in AP features. This suppressive effect of LFS depended on the LFS pulse number, such that application of 900 pulses of LFS had a stronger recovery effect on AP features that changed during EA compared to 600 pulses of LFS. The constructed phase plots of APs revealed that LFS at 900 pulses significantly decreased the changes in resting membrane potential [RMP], peak amplitude, and maximum rise and decay slopes that appeared during EA
Conclusion: Increasing the numbers of LFS pulses can magnify its inhibitory effects on EA-induced changes in AP features
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
Subject(s)
Animals, Laboratory , Male , CA1 Region, Hippocampal , Pyramidal Cells , Inhibitory Postsynaptic Potentials , Excitatory Postsynaptic Potentials , Seizures/therapy , Rats, WistarABSTRACT
Background and purpose: Nowadays repeated transcranial magnetic stimulation [rTMS] is being used as a treatment for some neurological disorders, but its effect on neuronal activity and synaptic plasticity has not been completely determined. The purpose of this study was to evaluate the effect of chronic rTMS on the ability of synaptic plasticity.
Materials and Methods: rTMS was applied to the hippocampal region for 14 days. One week following termination of rTMS, the amount of synaptic long-term potentiation [LTP] in animals was investigated and compared with control group. High-frequency stimulation [HFS] was applied to the perforant path for LTP induction, andfield potentials were recorded from granular layer of the dentate gyrus. Baseline field potential was recorded 10 minutes before HFS. An increase of at least 20% in population spike amplitude was measured as an index of synaptic potentiation.To compare the effects of rTMS on measured parameters, we used t-test and two way ANOVA followed by Benferroni test [Prism 8 software].
Results: Obtained data showed that, following 14 days of rTMS application causeda reduction in population spike amplitude compared to the control group [P<0.05].In addition, the ability of neurons generating LTP was reduced compared to the control group [P<0.001]. Paired pulse index measurement also showed thatthe paired-pulse facilitationdid not change following LTP induction in animals whom had received rTMS. However, there was a decrease in paired pulse facilitation in control group.
Conclusion: Chronic rTMS application reducesthe amount of synaptic potentiation. Considering the important role of LTP in the occurrence of cognitive processes, patterns of rTMS that have less effects on the ability of synaptic plasticity should be found.
ABSTRACT
Background: Low frequency stimulation [LFS] has been recently suggested as an antiepileptic method in treating the drugresistant epileptic syndromes such as temporal lobe epilepsy. So far, in the most clinical and experimental studies, LFS has been applied to the seizure focus itself. Considering the role of dentate gyrus in spreading of the limbic seizures, in the present study the effect of LFS of dentate gyrus on amygdala kindling-induced seizures was investigated
Materials and methods: To kindle the animals, using stereotaxic instrument, a tripolar electrode was inserted into right basolateral area of amygdala and a bipolar electrode was ipsilaterally placed in dentate gyrus of male Wistar rats. After a 10 days recovery period, animals divided into two groups. The animals of kindled group were received daily electrical stimulations. In kindled+LFS group, LFS was delivered to dentate gyrus 1 min after cessation of amygdala kindling stimulation. The maximum seizure stage and duration of afterdischarges were evaluated after kindling stimulation. The effect of LFS on behavioral seizure stages and afterdischarges was compared using Kruskall Wallis and repeated measures 2-way AVOVA. A P value less than 0.05 was considered as significant level
Results: The required time to achieve a stage 5 seizure was 12 days in kindled group animals. However, animals of kindled+LFS group did not show more than stage 2 seizure following 12 days of stimulation. LFS of dentate gyrus significantly prevented the increment of behavioral seizure stages and afterdischarge duration in kindled-LFS group compared with kindled group
Conclusion: The results of this study demonstrated that application of LFS in the dentate gyrus can be an effective therapeutic method for controlling the amygdala kindling-induced seizures. Furthermore, this study provide further evidences showing LFS of brain areas involved in spreading the seizures, other than seizure focus can have anticonvulsant affect