Basal Ganglia Mechanisms in Seizure Control

The basal ganglia comprise a set of interconnected subcortical nuclei that traditionally regulate motor planning and behavioural selection. In recent years, these structures have emerged as critical regulators of epileptic activity, exerting both pro- and anti-convulsant influences through complex inhibitory and excitatory circuits. GABAergic outputs from the substantia nigra pars reticulata and the ventral striatum modulate thalamocortical excitability, acting as a gating mechanism that can suppress seizure initiation or limit propagation. Conversely, disinhibitory pathways can amplify focal epileptic discharges, promoting secondary generalisation. Pharmacological and neuromodulatory interventions targeting nodes such as the subthalamic nucleus, nucleus accumbens and nigral-parafascicular projections have demonstrated significant antiseizure potential, offering new avenues for refractory epilepsy management. This convergence of circuit-level insight and translational innovation underscores the basal ganglia as both a focus for fundamental research and a compelling target for therapeutic development.

Research from Nature Portfolio

Recent studies have delineated a disinhibitory circuit linking the substantia nigra pars reticulata to the parafascicular nucleus that bidirectionally regulates temporal lobe seizure severity. Optogenetic activation of nigral parvalbumin-expressing GABAergic neurones projecting to the parafascicular nucleus was found to amplify seizure frequency and intensity in rodent models, whereas chemogenetic inhibition of the same pathway markedly attenuated epileptic discharges. Electrophysiological mapping confirmed that nigral outputs directly inhibit parafascicular GABAergic cells, uncovering a long-range disinhibitory loop whose modulation can either suppress or exacerbate seizure activity. These findings provide a refined circuit blueprint for targeted interventions designed to restore inhibitory balance in drug-resistant epilepsy.

Basal Ganglia Mechanisms in Seizure Control publication trend

The graph below shows the total number of articles in basal ganglia mechanisms in seizure control across all publications each year (not limited to Nature Index journals).

Technical terms

Basal ganglia: A group of subcortical nuclei involved in motor control, behavioural selection and modulation of cortical excitability.

Substantia nigra pars reticulata (SNr): The principal GABAergic output nucleus of the basal ganglia that projects to thalamic and brainstem targets to regulate inhibition.

Subthalamic nucleus (STN): A glutamatergic nucleus within the indirect pathway of the basal ganglia that influences SNr output and overall circuit excitability.

Nucleus accumbens shell (NAc shell): The ventral striatal region comprising medium spiny neurones that modulate reward, motivation and seizure propagation.

Convection-enhanced delivery: A technique for direct intracerebral infusion of pharmacological agents that circumvents the blood–brain barrier to achieve high local drug concentrations.

References

1. Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations. Frontiers in Bioengineering and Biotechnology (2024).
2. A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy. Nature Communications (2020).
3. Nucleus accumbens shell modulates seizure propagation in a mouse temporal lobe epilepsy model. Frontiers in Cell and Developmental Biology (2022).
4. Acute and chronic convection-enhanced muscimol delivery into the rat subthalamic nucleus induces antiseizure effects associated with high responder rates. Epilepsy Research (2023).