Abstracts

Rationale: The development of an independent epileptic focus in an area of the brain contralateral to the primary epileptic focus has been observed before. This mirror focus typically evolves over days in the experimental setting after status epilepticus or electrical kindling of the primary focal region. In contrast, we observed the rapid development of an apparent mirror focus in the contralateral hippocampus following microinjection of Kainic acid (KA) in the ipsilateral hippocampus in rats and sought to gain a better understanding of its underlying dynamics and neurotransmitter-mediated mechanisms using multisite intracranial recordings. Methods: Local field potentials (LFPs) were recorded in anesthetized rats using electrodes implanted in the CA3 region of both hippocampi and in the anteromedial nucleus of the thalamus of adult male rats. Epileptogenesis was induced in the rats with a microinjection of KA in the ipsilateral CA3 region. Development of seizure dynamics was followed under three experimental perturbations to the contralateral hippocampus: (A) no treatment (n=18), (B) pre-treatment with microinjection of the AMPA/Kainate receptor antagonist CNQX (n=15), and (C) pre-treatment with microinjection of the selective Kainate receptor antagonist UBP 301 (n=16). Results: Both the control and the UBP 301 groups had seizures preferentially originate from the hippocampus contralateral to the injection site and appearing within ten minutes of KA injection. In contrast, the CNQX group had seizures preferentially originate from the ipsilateral hippocampus. By tracking the order of seizure onset between the three recording sites, it was observed that the probability that a hippocampal seizure would propagate across commissural fibers prior to any thalamic seizure activity was significantly reduced in the CNQX group when compared to the control and UBP groups suggesting that the AMPA receptor mediated component responsible for mirror focus development was also necessary for the spread of ictal activity via the commissural fibers. Conclusions: Epilepsy is largely a network phenomenon of the brain which, because of the vast variability in which seizures arise, makes it difficult to treat. Understanding how a complex circuit in the brain develops, such as in the case of a mirror focus, may be critical to uncovering ways of either disrupting its development or treating its effects. The rapid appearance of a contralateral mirror focus via AMPA receptors in a limbic epilepsy model might be the mechanism by which a putative long-term mirror focus is established in vivo and may also underlie how secondary generalization progresses in some cases.