Altered Firing Rates and Patterns in Interneurons in Experimental Cortical Dysplasia

Cortical dysplasia (CD) is associated with severe epilepsy in humans, and the in utero irradiation of fetal rats provides a model of this disorder. These animals show a selective loss of inhibitory interneurons, and the surviving interneurons have a reduced excitatory synaptic drive. The current study was undertaken to see how alterations in synaptic input would affect spontaneous firing of interneurons in dysplastic cortex. We recorded spontaneous action potentials and excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) from somatostatin (SST)-, parvalbumin (PV)-, and calretinin (CR)-immunoreactive (ir) interneurons. We found that SST- and PV-ir interneurons fired less frequently and with less regularity than controls. This corresponded to a relative imbalance in the ratio of EPSCs to IPSCs that favored inhibition. In contrast, CR-ir interneurons from CD showed no differences from controls in spontaneous firing or ratio of EPSCs to IPSCs. Additional studies demonstrated that synaptic input had a powerful effect on spontaneous firing in all interneurons. These findings demonstrate that a relative reduction in excitatory drive results in less active SST- and PV-ir interneurons in irradiated rats. This would further impair cortical inhibition in these animals and may be an important mechanism of epileptogenesis.