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The Journal of Neuroscience, March 1, 2002, 22(5):2012-2021

Local Generation of Fast Ripples in Epileptic Brain

Anatol Bragin^{1, 3}, Istvan Mody^{1, 3}, Charles L. Wilson^{1, 3}, and Jerome Engel Jr^{1, 2, 3}

Departments of ¹ Neurology and ² Neurobiology and the ³ Brain Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90095

Aperiodic high-frequency oscillations (>100 Hz) reflect a short-term synchronization of neuronal electrical activity. It has been shown in the epileptic brain that spontaneous oscillations in the frequency range of 250-600 Hz reflect action potential population bursts of synchronously discharging neuronal clusters. These oscillations occur in the early stages of epileptogenesis in areas adjacent to the brain lesion and may trigger the formation of seizure-generating neuronal networks. We studied the extent of the area generating oscillations in the frequency range of 250-600 Hz [fast ripples (FRs)] in intrahippocampal kainic acid-treated rats with spontaneous seizures, by analyzing voltage versus depth profiles of FRs in hippocampal and parahippocampal areas in freely moving animals and by spatial mapping in hippocampal slice preparations in vitro. The strength of inhibition was compared in areas with and without FRs using a paired-pulse paradigm. The extent of the areas generating FRs did not exceed 1 mm³. The areas generating FRs became broader after the application of the GABA_A receptor antagonist bicuculline. Paired-pulse fast inhibition at 15-30 msec intervals was similar in areas generating FRs and areas not generating FRs. Our data illustrate that hypothesized clusters of highly interconnected neurons are capable of overcoming interneuron feedback inhibition, resulting in generation of epileptiform bursts, eventually leading to seizure activity.

Key words: hippocampus; entorhinal cortex; chronic seizures; fast ripples; kainic acid; oscillation

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2252012-10$05.00/0

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