Study On The Regulation Of Absence Epilepsy With Gabazine And Snr Lesion

Absence epilepsy(AE)is a common clinical neurological disease.Usually AE is characterized with the 2-4Hz spike-wave discharges(SWDs)and is highly associated with the abnormal interactions in the cortico-thalamic system.Recently the basal ganglia(BG)has been suggested to participate in the bidirectional modulation of SWDs through two distinct pathways based on the computational model.Both the projection pathway from substantia nigra pars reticulate(SNR)in basal ganglia to thalamus(the SNRthalamus pathway)and the directed inhibitory pathway from globus pallidus external segment(GPe)to cortical cortex(GPe-Ctx pathway)could regulate the burst of SWDs.However,all these studies lack the evidence from electrophysiological experiments.Based on the results from computational neuroscience,we assessed the mechanism of how BG regulates the absence epilepsy with well-established GBL-induced AE rat models.For this purpose,we injected Gabazine into GPe to excite the GPe neurons which could suppress the GPe-Ctx pathway and destroyed the SNR by electrical lesion which could block the SNR-thalamus pathway separately.The main contents and findings in this thesis are summarized as follows:1.Both injecting Gabazine into GPe and destroying the SNR could suppress the seizure time of SWDs through reducing the averaged seizure time of SWDs rather than reducing the seizure frequency of SWDs.Furthermore,the GPe-Ctx pathway may play a more critical role in regulating AE than SNR-thalamus pathway for that exciting GPe neurons suppressed more seizure time of SWDs than damaging SNR.2.Consistent with prior studies,the rhythm of SWDs in GBL-induced AE rats during seizures was about 4Hz in our study.However,this original rhythm of SWDs was changed by injecting Gabazine into GPe,which performed as a higher rhythmic SWDs(more than 4Hz)followed by a slower rhythmic SWDs(about 4Hz)during seizures.This emerging seizure pattern suggested that the GPe-Ctx pathway may regulate and control AE through changing the rhythm of SWDs.Unlike Gabazine intervention,blocking the SNRthalamus pathway did not change the rhythm of SWDs.After electrolytic destroying the SNR,the waveform of SWDs did not showed a typical alteration between spike and slow wave during seizures,which became out of order,suggesting that SNR may play an important role in the configuraion of SWDs.The SNR-thalamus pathway may regulate AE through influencing the formation of SWDs.Meanwhile,neuron spike analysis showed that the firing rate of the cortex or thalamus was higher than normal state during seizures under both interventions and the firing rate was positive correlated with the rhythm of SWDs.3?The information flow in the cortex-thalamus cycle was significantly increased during seizures,implying a high relationship between SWDs and the abnormal interaction in the cortex-thalamus cycle.After Gabazine intervention,the information flow from thalamus to cortex increased,while information flow between SNR and thalamus were depressed during seizures,indicating that Gabazine intervention regulated and controlled AE mainly by changing the activity in the thalamus and the abnormal activity of the thalamus may result in the change of SWDs rhythms.After electrolytic lesion of SNR,the information flow from cortex to thalamus increased during seizures,suggesting that SNR may excite the activity of cortex and increase the relationship from cortex to thalamus to suppress SWDs.In summary,we used GBL-induced absence epilepsy rat model to verify that the projection pathway from GPe to the cortex and the projection pathway from SNR to cortex through thalamus could regulate and control SWDs with electrophysiological experiments.Meanwhile,we revealed the underlying mechanisms of how these two projection pathways regulated SWDs.Our results not only increased the understanding of generation and regulation of absence seizures,but also provided a theoretical basis for the clinical treatment of absence epilepsy.