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Review
. 2020 Dec 2:14:581826.
doi: 10.3389/fnsys.2020.581826. eCollection 2020.

Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy

Sonja Bröer  1
Affiliations
Review

Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy

Sonja Bröer. Front Syst Neurosci. .

Abstract

The most researched brain region in epilepsy research is the temporal lobe, and more specifically, the hippocampus. However, numerous other brain regions play a pivotal role in seizure circuitry and secondary generalization of epileptic activity: The substantia nigra pars reticulata (SNr) and its direct input structure, the subthalamic nucleus (STN), are considered seizure gating nuclei. There is ample evidence that direct inhibition of the SNr is capable of suppressing various seizure types in experimental models. Similarly, inhibition via its monosynaptic glutamatergic input, the STN, can decrease seizure susceptibility as well. This review will focus on therapeutic interventions such as electrical stimulation and targeted drug delivery to SNr and STN in human patients and experimental animal models of epilepsy, highlighting the opportunities for overcoming pharmacoresistance in epilepsy by investigating these promising target structures.

Keywords: GABA; basal ganglia; epilepsy; focal therapy; propagation; seizure; substantia nigra (SN); subthalamic nucleus (STN).

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Conflict of interest statement

SB is a shareholder of Neurona Therapeutics Inc.

Figures

Figure 1
Figure 1
Potential routes of seizure propagation in temporal lobe epilepsy, modified from Löscher et al. (2008). Seizures that arise in the limbic system can be propagated via the cortex, basal ganglia (yellow), thalamic nuclei and midbrain and brain stem nuclei and generalize across the whole brain. Red, GABAergic transmission; blue, glutamatergic transmission; black, other chemically composite pathways.
See this image and copyright information in PMC

References

    1. Alexander G. E., Crutcher M. D. (1990). Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 13, 266–271. 10.1016/0166-2236(90)90107-L - DOI - PubMed
    1. Al-Otaibi F. A., Hamani C., Lozano A. M. (2011). Neuromodulation in epilepsy. Neurosurgery 69, 957–979. 10.1227/NEU.0b013e31822b30cd - DOI - PubMed
    1. Backofen-Wehrhahn B., Gey L., Bröer S., Petersen B., Schiff M., Handreck A., et al. (2018). Anticonvulsant effects after grafting of rat, porcine, and human mesencephalic neural progenitor cells into the rat subthalamic nucleus. Exp. Neurol. 310, 70–83. 10.1016/j.expneurol.2018.09.004 - DOI - PubMed
    1. Banerjee P. N., Hauser R. A. (2008). Incidence and Prevalence, in Epilepsy: A Comprehensive Textbook, eds. Engel J. J., Pedley T. A. (Philadelphia: Lippincott Williams & Wilkins; ), 48.
    1. Baraban S. C., Southwell D. G., Estrada R. C., Jones D. L., Sebe J. Y., Alfaro-Cervello C., et al. (2009). Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc. Natl. Acad. Sci. U. S. A. 106, 15472–15477. 10.1073/pnas.0900141106 - DOI - PMC - PubMed