Abstracts

Cortical dysplasia (CD) has a strong clinical association with epilepsy. We have studied an animal model of CD, in utero irradiation in rats. Previous studies have shown that the frequency of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons in dysplastic cortex is decreased compared with control cortex. A reduction in excitatory drive on interneurons could contribute to this impairment of inhibition. The purpose of the present study is to address this hypothesis by measuring spontaneous and miniature excitatory postsynaptic currents (EPSCs) in fast spiking (FS) interneurons in dysplastic and control neocortex. Pregnant rats were exposed to 225 cGy of external [gamma]-irradiation at E17. The offspring consistently demonstrated diffuse CD. Whole-cell recordings were performed in neocortical slices from irradiated and control rats at age 21-28 d. Interneurons were identified by their morphology and firing pattern to suprathreshold current pulses. Data was obtained from interneurons showing high frequency action potentials with no or little adaptation (i.e., FS interneurons). We compared the frequency and amplitude of sEPSCs and mEPSCs from irradiated and control animals. We also assessed short-term plasticity (STP) of stimulus-evoked EPSCs using a 5-pulse stimulation protocol (20 Hz). The frequency of sEPSCs and mEPSCs was decreased in FS internurons in CD. The amplitude and kinetics were not different. On average, the frequency of sEPSCs was 0.9 [plusmn] 0.2 Hz in CD (n = 16) and 4.8 [plusmn] 0.7 Hz in control tissue (n = 11; p[lt]0.01). sEPSC amplitude was 13.3 [plusmn] 0.9 pA in CD and 13.6 [plusmn] 1.1 pA in control tissue (p[gt]0.05). The frequency of mEPSCs was 0.2 [plusmn] 0.1 Hz in CD (n =8) and 0.7 [plusmn] 0.2 Hz in control tissue (n = 5; p[lt]0.01). STP showed depression in every interneuron in control, but a mixture of depression and facilitation among cells in CD. On average, the ratio of the second response to the first was 73 [plusmn] 8.6 percent in control tissue (n =7), but 107 [plusmn] 11.6 percent in CD (n = 8; p[lt]0.05). Our results show that the excitatory driving force, namely sEPSCs and mEPSCs, in FS interneurons in CD is largely attenuated. The absence of change in the amplitude and kinetics of sESPCs and mEPSCs implies a presynaptic locus. Reduced short-term depression of evoked EPSCs in CD interneuron indicates that a decrease in release probability of the presynaptic terminal could contribute to this reduced excitatory drive. Reduced numbers of excitatory contacts are another possible mechanism. This study further documents impairments in the inhibitory component of the neocortical circuitry in radiation-induced CD. (Supported by a grant from NINDS (2R01NS35651) to SNR.)