Abstracts

RATIONALE: Cortical dysplasia has a strong association with epilepsy but the exact relationship between the structural abnormalitlies in this disorder and the physiologic abnormailites that produce epilepsy are poorly understood. In utero irradiation of rats produces diffuse cortical dysplasia, neuronal heterotopia in the cortex and hippocampus, and agenesis or hypoplasia of the corpus callosum. Previous studies in this model have demonstrated a selective reduction in the density of inhibitory interneurons in dysplastic cortex (DC)(Roper et al., 1999). This study examined alterations in cortical circuitry by quantifying spontaneous postsynaptic currents in pyramidal cells from dysplastic and control neocortex. METHODS: Pregnant rats were exposed to 225 cGy external ?-irradiation on gestational day 17. Experiments were performed on irradiated and control offspring at 28-35 days of age. Whole cell patch clamp recordings were obtained from visualized pyramidal cells in dysplastic and control neocortex in 300 ?m-thick coronal hemispheric slices. RESULTS: Spontaneous inhibitory postsynaptic currents (IPSC's) were significantly decreased in amplitude and frequency in pyramidal cells from DC. Miniature IPSC's (obtained during exposure to tetrodotoxin to abolish action potential-dependent activity) were not changed in amplitude but signficantly reduced in frequency in pyramidal cells from DC. Spontaneous excitatory postsynaptic currents (EPSC's) were signficantly increased in amplitude and frequency in DC; but miniature EPSC's showed no difference between pyramidal cells from dysplastic and control neocortex. CONCLUSIONS: These results demonstrate a significant impairment in inhibition in DC. Miniature IPSC results suggest that the impairment is primarily presynaptic and are consistent with previous reports of a decreased density of inhibitory neurons in DC in this model and in human surgical specimens. Spontaneous, but not miniature, EPSC's are increased in DC and this could be secondary to reduced inhibition or an increased proportion of excitatory bursting neurons. This work was supported by an NINDS grant to SNR (NS35651).