Abstracts

RATIONALE:_ Cortical Dysplasia is characterized by anatomical malformations of the cerebral cortex. Alterations in glutamate or GABA receptor expression have been invoked to explain the epileptogenicity of dysplastic cortex. We examined spontaneous postsynaptic activity mediated by activation of glutamate (Glu) or GABA receptors (R) in dysplastic cerebral cortex, resected to treat catastrophic epilepsy in children (0.2 to 14 years). METHODS: Neurons were visualized in slices by Nomarski optics and infrared videomicroscopy and voltage clamp recordings were made. Patch pipettes (4-6 M?) contained a Cesium Methanesulfonate based internal solution. GluR mediated synaptic activity was isolated by adding bicuculline (20 uM), while GABA-R mediated synaptic activity was isolated by adding CNQX (10 ?M)and APV (100 ?M). RESULTS: Many neurons displayed spontaneous synaptic currents mediated by activation of both GluRs and GABA-Rs. In younger cases, activity mediated by GABA-Rs predominated. In some cases, spontaneous activity was almost exclusively GABAergic. CONCLUSIONS: Neurons from dysplastic cortex receive inputs capable of activating both GluRs and GABA-Rs, and reduced inhibition is probably not a likely explanation for the epileptogenicity of dysplastic human cortex. However, a potential excitatory role or increased synchronization of synaptic activity mediated by GABA-Rs, especially in very young cases, could be considered. Supported by USPHS NS 28383, 38992, and 36536.