Analysis Of The Electrical Activitiy Characteristics Of The Substantia Nigra Pars Reticulata Anterior In Amygdala Kindling Epilepsy Model In Mice

Epilepsy is a common chronic neurological disorder,and the patients with refractory epilepsy always cannot get effective treatments from antiepileptic drugs.Therefore,it is of great significance to figure out the mechanism of the initiation,development and termination of the refractory epilepsy and the key therapeutic targets in clinical.Temporal lobe epilepsy(TLE)is one of the most common intractable epilepsies in adults.For a long time,the limbic structures such as the hippocampus and amygdala are believed to the key brain structures involved in TLE.In recent years,clinical and experimental studies demonstrated that the substantia nigra pars reticulata anterior(SNr_a)also plays an important role in the initiation,development and termination of the TLE.However,most of the results are from neuropharmacological studies,the electrophysiological investigations of the SNr_a are still rare for TLE.In this study,we built the amygdala kindling epilepsy model in mice and recorded the neural activities from the right basolateral amygdala(BLA)and the SNr_a by using the multi-channel in vivo recording techniques.We analyzed the neural activitity characteristics of the two regions during the seizures,and computed the directionality index dynamics of the information flow between the BLA and the SNr_a.At last,we conducted the SNr_a lesion experiments to further investigate the role of the SNr_a in amygdala kindled seizures.The main results of this study include:(1)The information flow from the SNr_a to the BLA became dominant during the clonic-like period of the amygdala kindled stage 5seizures,and this phenomenon was not found during the other periods of the stage 5seizures and the seizures of the other stages.This hints that the SNr_a has regulatory effects during the clonic-like periods of the amygdala kindled stage 5 seizures.(2)We analyzed the firing rate and the peak value of autocorrelation function(ACF)of neurons recorded in the BLA and SNr_a.We found that the firing rate of the neurons recorded in the BLA was higher in fully-kindled mice,but there were no significant differences in the peak value of ACF between the not-fully-kindled and fully-kindled mice.In addition,there were no significant differences in the firing rate and peak value of ACF of neurons recorded from the SNr_a between the not-fully-kindled and fully-kindled mice.(3)In fully-kindled mice,the SNr_a lesion prelonged the stage 5 seizures’afterdischarge(AD),which were mostly attributed to the prolonged clonic-like periods.The clonic period of seizures is closely related with the termination of seizures,and the longer clonic period represents the weaker anti-convulsant ability.Therefore,the SNr_a may play an anti-convulsant role in amygdala kindled stage 5 seizures.In summary,we investigated the role of the SNr_a in amygdala kindled seizures using the electrophysiological and computational study.The results suggest that the SNr_a may play an anti-convulsant role in the amygdala kindled seizures.This study contributes to the understanding of seizure spread and termination in TLE and may,to some extent,be meaningful for the selection of therapeutic targets and development of antiepileptic drugs for clinical refractory epilepsy.