Role of the claustrum in kindling of generalized seizures

Date

2017-12-21

Authors

Mohapel, Paul

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Abstract

The precise neuroanatomical pathways underlying seizure genesis and propagation are largely unknown. Current evidence suggests that epileptiform activity may travel along preferred anatomical routes and that some structures may act as “gates” that funnel and spread seizure activity throughout the brain. Burchfiel and Applegate (1989a) have proposed a gating hypothesis to explain kindled seizure propagation. According to this hypothesis, kindling involves three distinct phases that are separated by two crucial gates. The first gate mediates the expression of partial seizures, and the second gate mediates the expression of fully generalized seizures. Little work has been done in determining which anatomical sites contain these gates, in particular the second gate. The following experiments set out to investigate the role that the claustrum may play in mediating the second gate, responsible for the expression of kindled generalized seizures. Experiments 1 and 2 utilized correlative strategies to address the claustrum's participation in kindling. In Experiment 1, kindling was evoked directly from claustrum and these properties were compared with the nearby structures of the amygdala, insular cortex, and perirhinal cortex. The claustrum generally exhibited much more potent epileptogenic attributes than the other structures, including quick progression to seizure generalization and more vigorous and sustained convulsions. However, the claustrum, shared many electrographic and convulsive properties with the insular and perirhinal cortices, including a two phase development of generalized seizures, rapid progression to seizure generalization, and quick onset to limb convulsions. In Experiment 2, further dissociations were detected between claustrum and amygdaloid kindling by changes in molecular products linked with neural plasticity. Claustrum kindling was associated with generally more intensive expression of claustrum in kindling. Experiments 3 and 4 used more direct approaches to address the role of the claustrum in kindling. In Experiment 3, alternating stimulation between the claustrum and amygdala demonstrated that the claustrum was capable of arresting amygdaloid kindling at the partial seizure stages. This kindling antagonism effect was not observed with stimulation of the superficial insular cortex, perirhinal cortex, or piriform cortex. In Experiment 4, lesions applied to the claustrum were effective in delaying, but not blocking amygdaloid kindling. These delays were in amygdaloid kindling were produced by small lesions restricted to the ipsilateral anterior claustrum. Taken together these data suggest that the claustrum may represent the crucial mediator of the second gate responsible for kindled seizure generalization.

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Keywords

Claustrum, Convulsions

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