Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence

Abstract

Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder.

Control of absence seizures induced by the pathways connected to SRN in corticothalamic system

“…Our results complement the recent findings on controlling the absence seizures as obtained in Ref. (Chen et al 2014). …”

“…Here, we still use the meanfield model developed in Ref. (Chen et al 2014). The studied network model contains nine neural populations as shown in Fig.…”

“…Some existing experimental results can support this viewpoint (Biraben et al 2004;Deransart and Depaulis 2002). However, due to the complicated interactions between the basal ganglia and corticothalamic, the mechanism on how the activities of the basal ganglia influence absence seizures in corticothalamic circuit is still unclear (Chen et al 2014).…”

“…In particular, main question involved in the present study is how to control SWDs in the corticothalamic system with changing projection strength of different pathways. Recently, Chen et al (2014) used a mean-field model to study the precise roles of some direct basal ganglia-thalamic pathways in controlling absence seizures, where SWDs were induced by the inhibitory projection from TRN to SRN and the delay, which is related to the slow kinetics induced by GABA B receptors in the SRN. However, the factors of the absence seizure activity in the corticothalamic circuit are not only limited to the inhibitory pathway (Crunelli and Leresche 2002;Marten et al 2009;Paz et al 2011).…”

“…To further understand the seizure and mediating mechanisms of absence epilepsy in the brain, we will use the mean-field model containing the corticothalamic circuit and basal ganglia as developed in Chen et al (2014) to study control of absence seizures. We find that absence seizures can also be induced by excitatory projections from excitatory pyramidal neurons to SRN or conversely, or through the excitatory pathway from SRN to TRN.…”