Abstracts

RATIONALE: Taylor type, focal cortical dysplasia (FCD) corresponds to a localized disruption of cortical lamination with large, aberrant neurons. FCD patients present with medically intractable epilepsy, and thus they become candidates for surgical treatment. Histochemical analysis of surgically resected, human FCD tissue has shown an abnormal distribution of NMDA receptors and a decrease of presumptive interneurons that can, however, provide an increased number of GABAergic terminals surrounding principal cells (Spreafico et al. [italic]Neurology[/italic] 50:27, 1998). We have also found that FCD tissue slices maintained in vitro respond to 4-aminopyridine (4AP) application by generating NMDA receptor-mediated ictal discharges along with GABA receptor-mediated potentials (Avoli et al. [italic]Ann Neurol[/italic] 46: 816, 1999). Here, we tried to determine whether and how GABA receptor-mediated mechanisms lead to ictogenesis in FCD tissue.
METHODS: We used field potential and [K⁺][sub]o [/sub] recordings in slices obtained from FCD and (for comparison) from temporal lobe epilepsy (TLE) patients. The latter tissue does not present any obvious structural abnormality. 4AP (50-100[mu]M), the GABA[sub]A[/sub] receptor antagonist bicuculline methiodide (BMI, 10[muM) and glutamatergic receptor antagonists were bath applied.
RESULTS: Ictal discharges (duration[gt]10s) were readily induced by 4AP (n=12 slices), while BMI (n=3) only disclosed brief ([lt]3s) epileptiform discharges. Moreover, during 4AP application ictal discharges were shortly preceded (and thus triggered) by presumptive GABA receptor-mediated synchronous potentials. Ictal discharges were never seen in TLE slices that, however, generated GABA receptor-mediated potentials. These events persisted during blockade of glutamatergic transmission in both FCD and TLE slices and were associated with elevations in [K⁺][sub]o [/sub]up to 6.5 and 4.2mM, respectively.
CONCLUSIONS: Our findings suggest that epileptiform activity in FCD tissue is initiated by a rather novel synchronizing mechanism that paradoxically relies on the activation of GABA receptors and leads to increases in Our findings suggest that epileptiform activity in FCD tissue is initiated by a rather novel synchronizing mechanism that paradoxically relies on the activation of GABA receptors and leads to increases in [K⁺][sub]o [/sub]that are larger in FCD tissue. that are larger in FCD tissue.
[Supported by: Canadian Institutes of Health Research and Savoy Foundation.]