Research On The Direct Pallido-frontal Cortex Pathway Regulating And Controlling Absence Epilepsy

Epilepsy is a paroxysmal behavior caused by abnormal,excessive or hypersynchronous discharges of neurons in the brain.Absence epilepsy(AE)is a subtype of idiopathic generalized epilepsy and experimental studies showed that a typical attack of absence seizures commonly causes a sudden onset and offset of 2-4 Hz spike-wave activities,accompanying with temporary loss of consciousness.Recently studies have proved that the Substantia pars reticulate(SNr)can transmit information through direct connection with superior colliculus and ventromedial thalamic to the cerebral cortex,which suggests that the SNr could modulate the neural activity of corticothalamic network.Anatomically,the Globus pallidus externa(GPe)can affect the neural activity of the SNr through two different pathways,including the GPe-SNr and GPe-subthalamic neucleus(STN)-SNr pathways,which indicate that the GPe could modulate the neural activity of corticothalamic network through these pathways.Recently,animal experiments have identified that the existence of a direct efferent output from the GPe to both excitatory pyramidal neurons and inhibitory interneurons in the cerebral cortex.Furthermore,a computational modeling investigation found that this direct pallido-prefrontal cortex pathway might participate in the control of absence seizures.However,this finding is still lacking the direct animal or clinical experimental evidence.In this work,we established the GBL-induced absence epilepsy rat model.we damaged SNr by electrical lesion to block SNr-thalamic-cortex pathway.Furthermore,injecting GABA receptor antagonist gabazine in GPe can enhance the excitability of GPe neurons and directly modulate neural activities of the cerebral cortex.To detect Spike and wave discharges(SWDs),we use large scale variance analysis algorithm and time-frequency analysis algorithm.These findings might provide some direct experimental evidence to support the concept that the pallido-cortical pathway could modulate absence seizures.The main contents and findings in this thesis are listed in the following.1.In the GBL-induced absence epilepsy rat model,the time of absence seizures in the prefrontal motor cortex was significantly reduced within 15 45 minutes after injecting gabazine in GPe.It suggests that GPe neuronal activity may play an important role in the regulation of ansence seizures.2.In the GBL-induced absence epilepsy rat model,we damaged SNr by electrical lesion can significantly suppress the time of absence seizures in the prefrontal motor cortex.During the ictal period of 15 to 35 minutes,the contribution of GPe and SNr suppressing the generation 2 4 Hz SWDs are 47.2% and 34.6%.Compared with SNr,GPe might play more critical roles in regulating and controlling absence epilepsy.3.During the ictal period of 10 to 45 minutes,the time of absence seizures of rats both injected gabazine in GPe and damaged SNr is shorter than those only injected gabazine in GPe.This suggests that,beside the traditional GPe-nigro-cortex pathways,the direct pallido-prefrontal cortical pathway is another way regulating and controlling absence epilepsy.4.We compared and analyzed the absence seizure frequency and the average time of absence seizure at different periods of time in the GBL-induced absence epilepsy rat model.The absence seizure frequency could be used to characterize the intensity of absence seizures.5.The information entropy of EEG signals at different periods of time in the GBL-induced absence epilepsy rat model was compared and analyzed.It was found that the information entropy of the corresponding EEG signals will decrease when the absence seizures reduced;the information entropy of the corresponding EEG signals increased as the absence seizures increased.It is suggested that information entropy might characterize the SWDs during the time of absence seizures.6.By analyzing the power spectrum and synchronization of EEG signals under different experimental conditions.It was found that the power spectrum and synchronization of EEG was mainly characterized by a frequency band of 1-8 Hz during the time of absence seizures.Further,injecting gabazine into GPe and damaging SNr had more influence on the power spectrum and synchronization of 1-8 Hz.In summary,our animal experiments have demonstrated that the direct GABAergic pallido-prefrontal cortical pathway plays a critical role in controlling and regulating absence seizures.Furthermore,GPe may play a more important role in the regulation of absence seizures than SNr.These findings provide more direct insights into principles and mechanisms of absence seizures and offer evidence to support the results of computational modeling.