INCREASED EXCITABILITY AND INWARD RECTIFICATION IN LAYER-V CORTICAL PYRAMIDAL NEURONS IN THE EPILEPTIC MUTANT MOUSE STARGAZER

The excitability of layer V cortical pyramidal neurons was studied in vitro in the single-locus mutant mouse stargazer (stg), a genetic mode l of spike wave epilepsy. Field recordings in neocortical slices from mutant mice bathed in artificial cerebrospinal fluid revealed spontane ous synchronous network discharges that were never present in wild-typ e slices. Intracellular and whole cell recordings from stg/stg neurons in deep layers showed spontaneous giant depolarizing excitatory posts ynaptic potentials generating bursts of action potentials, and a 78% r eduction in the afterburst hyperpolarization. Whole cell recordings re vealed gene-linked differences in active membrane properties in two ty pes of regular spitting neurons. Single action potential rise and deca y times were reduced, and the rheobase current was decreased by 68% in mutant cells. Plots of spike frequency-current relationships revealed that the gain of this relation was augmented by 29% in the mutant. Co mparisons of visually identified pyramidal neuron firing properties in both genotypes revealed no difference in single action potential afte rhyperpolarization. Voltage-clamp recordings showed an approximately t hreefold amplitude increase in a cesium-sensitive inward rectifier. No cell density or soma size differences were observed in the layer V py ramidal neuron population between the two genotypes. These results dem onstrate an autonomous increase in cortical network excitability in a genetic epilepsy model. This defect could lower the threshold for aber rant thalamocortical spike wave oscillations in vivo, and may contribu te to the mechanism of one form of inherited absence epilepsy.