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 model of spike wave epilepsy. Field recordings in neocortical slices from mutant mice bathed in artificial cerebrospinal fluid revealed spontaneous synchronous network discharges that were never present in wild-type slices. Intracellular and whole cell recordings from stg/stg neurons in deep layers showed spontaneous giant depolarizing excitatory post-synaptic potentials generating bursts of action potentials, and a 78% reduction in the afterburst hyperpolarization. Whole cell recordings revealed gene-linked differences in active membrane properties in two types of regular spiking neurons. Single action potential rise and decay 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. Comparisons of visually identified pyramidal neurons firing properties in both genotypes revealed no difference in single action potential afterhyperpolarization. Voltage-clamp recordings showed an approximately threefold amplitude increase in a cesium-sensitive inward rectifier. No cell density or soma size differences were observed in the layer V pyramidal neuron population between the two genotypes. These results demonstrate an autonomous increase in cortical network excitability in a genetic epilepsy model. This defect could lower the threshold for aberrant thalamocortical spike wave oscillations in vivo, and may contribute to the mechanism of one form of inherited absence epilepsy.
Di Pasquale
E
E
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Keegan
K D
KD
Noebels
J L
JL
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003344:Cortical Synchronization; D004832:Epilepsy, Absence / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000503:physiopathology*