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.
Highlights
Absence epilepsy is a generalized non-convulsive seizure disorder of the brain, mainly occurring in the childhood years [1]
There is accumulating evidence that absence seizures are due to abnormal interactions between cerebral cortex and thalamus, and the basal ganglia may take part in controlling such brain disease via the indirect basal ganglia-thalamic pathway relaying at superior colliculus
We predicted that two direct inhibitory basal ganglia-thalamic pathways emitting from the substantia nigra pars reticulata may participate in the control of absence seizures
Summary
Absence epilepsy is a generalized non-convulsive seizure disorder of the brain, mainly occurring in the childhood years [1]. The basal ganglia receive multiple projections from both the cerebral cortex and thalamus, and in turn send both direct and indirect output projections to the thalamus. These connections enable the activities of the basal ganglia to influence the dynamics of the corticothalamic system. It is naturally expected that the basal ganglia may provide an active role in mediating between seizure and non-seizure states for absence epileptic patients Such hypothesis has been confirmed by both previous animal experiments [19,21,22,23] and recent human neuroimage data [20,24,25]. Due to the complicated interactions between basal ganglia and thalamus, the underlying neural mechanisms on how the basal ganglia control the absence seizure activities are still remain unclear
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