Investigation Of The Mechanisms Underlying The Inhibitory Effect Of Electrical Stimulation On Epilepsy In Rat Hippocampus

Deep brain stimulation is a hot spot in neurophysiology and neural engineering recently, especially the suppression effect of electrical stimulation in hippocampus on epilepsy. As we know, hippocampus is a very important area of learning and memory in the brain, and origin of many neural diseases. Therefore, it is significant to investigate the effect and mechanism of electrical stimulation in hippocampus.In this dissertation, we delivered electrical stimulation by self-made micro stimulating electrodes to the vertical hippocampus commissural (VHC) of rat, then we recorded the evoked population spikes (PS) and spontaneous spikes (MUA) in hippocampal CA3 region by high density recording sited micro electrode array. Upon the signals recorded above, we studied effects of different stimulating parameters (i.e. various frequency, intensity and duration) of electrical stimulation to normal and epileptic rat hippocampus. Also we discussed the mechanisms of electrical stimulation by analyzing the firing mode of spontaneous spikes of neurons at CA3 region and axons of VHC, as well as the efficacy difference of electrical stimulation in contralateral and ipsilateral hippocampal CA3 region.The main results of this dissertation were summarized as following:(1) The effect of high frequency stimulation on excitability of the normal hippocampusWe found continuous high frequency DBS in neural fibers (VHC) can suppress the population excitatory behavior of remote nucleus (CA3), and reduce the amplitude of PS and the firing frequency of MUA. This suppression effect is positive correlation to stimulating frequency, intensity and duration. The stimulating parameters that performed the best suppression effect are 100～125 Hz stimulating frequency,75% stimulating intensity and 30 s stimulating duration. Moreover, the suppression effect is reversible. Once we stopped delivering stimulation, the amplitude of PS and firing frequency of MUA would recover to the level prior to stimulation gradually.(2) The suppression effect of high frequency stimulation on epilepsy Through the application of DBS to the epileptic rat hippocampus, high frequency stimulation reduced the power of local field potentials (LFP) during ictal activity, decreased the firing of epileptic activity, and suppressed the development of epilepsy. Besides, we examed the efficacy of short pulse burst train that mimicked the firing pattern of LFP during interictal activity. The results showed that such electrical stimulation could also obviously reduce the power and intensity of LFP during interictal activity.(3) The mechanism of the suppression effect of high frequency stimulationThe results of local DC current stimulation showed that both neural fibers and neurons in the remote nuclei were strongly depolarized after high frequency stimulation, which induced great increase of extracellular potassium concentration. The mass opening of calcium modulated potassium channels could produce the effect of afterhyperpolarization (AHP), as therefore the long lasting suppression effect of high frequency stimulation on MUA may partly own to the action of AHP.In conclusion, this dissertation further demonstrated the significant suppression effect of high frequency stimulation on epilepsy through in vivo study. And the results of this dissertation provide some theoretical guide in clinical treatment for epilepsy, which is very significant to the development of new therapy for refractory epilepsy.