Investigation Of Stimulation Parameters And Mechanisms For Suppressing Epileptiform Activity By Closed-loop Deep Brain Stimulation In Rat Hippocampus

Because of the successful application of deep brain stimulation in neural disorder, suppressing epilepsy with deep brain stimulation has become a hot spot in neural engineering. Although deep brain stimulation already expresses great safety and effectiveness in the control of epilepsy, the stimulating parameters are waiting to be optimized. Moreover, the mechanism of deep brain stimulation is still unknown. Therefore, it is of great significant to investigate the appropriate stimulating parameters and possible mechanism of epileptiform activities’suppression.In this thesis, we used closed-loop electrical stimulation system to suppress seizure-like bursts on focal Picrotoxin model of rat hippocampal in CA1 region. Stimuli were applied on Schaffer collateral. We tried different stimulating parameters to suppress seizure-like burst. Moreover, mechanisms of high frequency stimulation were studies in normal rat and epileptic model rat. The main results were summarized as follows:(1) This thesis found out that the stimulating frequency higher than 100 Hz leaded to better seizure-like burst suppression. However, the higher frequency would cause more after discharge. Therefore, stimulation with frequency between 100-200 Hz could get better suppression for seizure-like burst and reduce after discharge. Moreover, the response time of stimulation less than 0.1 s would not have effects on the suppression of seizure-like burst, In addition, we controlled ital ativities lasting 30 s with closed-loop stimulation.(2) During orthodromic high frequency stimulation, neurons’firing pattern and rate changed a lot under different stimulating frequency. When stimulating frequency was between 20-100 Hz, interneurons could be entrained by stimulus, and their firing rates were stable during high frequency stimulation. Nevertheless, pyramidal cells could not be inhibited by interneurons, but be highly evoked during stimulation. Moreover, the longtime inhibition in low intensity stimulation was replaced by after discharge in high intensity stimulation. As a result, inhibition effect related with interneurons and GABAergic synapse might not be the mechanism of suppression for seizure-like bursts in this thesis.(3) We found that pyrimidal cells could not generate action potential during orthodromic high frequency stimulation in PTX rat model. The result testified that depolarizing blockade of pyramidal cell might be the reason of suppression for seizure-like bursts. Moreover, antidromic stimuli could also suppress seizure-like bursts, which also proved that depolarizing blockade caused by high frequency stimulation was one of main reasons of suppression for seizure-like bursts.In conclusion, the thesis found the appropriate stimulating parameters to suppress seizure-like bursts, and demonstrated that pyramidal cell’s depolarizing blockade might be the mechanism. These results provided theoretical guidences for clinical application of deep brain stimulation for epileptic suppression.