Epilepsia, 48(Suppl. 5):35–40, 2007 Blackwell Publishing, Inc. C  International League Against Epilepsy Status Epilepticus: Treatment, Outcomes, and Prophylaxis Voltage Depth Profiles of High-frequency Oscillations after Kainic Acid-induced Status Epilepticus Anatol Bragin, Charles L. Wilson, and Jerome Engel Jr. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Summary: High-frequency oscillations (HFOs) have been de- scribed in normal and epileptic brains of animals and humans. These oscillations reflect a short-term integration within neu- ronal networks and have important functional consequences for normal and pathological processes. We performed a compar- ative voltage depth profile analysis of normal and pathological HFOs after intrahippocampal kainic acid injection. Sixteen chan- nel recording probes, with 100–200 μm separation between the tips of microelectrodes, were implanted along the CA1—dentate gyrus axis in the anterior hippocampus of adult rats. Guide can- nulae were implanted in the CA3 area. After a week of baseline recording kainic acid (KA) (0.2μg/0.2μl) was injected into the CA3 area. Electrical activity continued to be record for the next 3–4 weeks after KA induced status epilepticus. Voltage depth profiles and power spectral analysis of HFOs were performed off-line using DataPac software. Ripple oscillations (80–200 Hz) in the CA1 area and gamma activity (40–80 Hz) in the dentate gyrus remained after status epilepticus. In the group of rats that later developed seizures a new pattern consisting of bursts of population spikes (BPS) occurred. The maximum of amplitude for BPS generated in CA1 was in the pyramidal layer and for those generated in the dentate gyrus was in the granular layer. BPS appeared 2–3 days after status epilepticus and remained for the rest of the experiments. The frequencies of intraburst spikes varied between 80 Hz and 600 Hz. With increasing distance from the area of the burst generation, this activity took on the appearance of HFOs. The occurrence of spontaneous BPS ap- pear to be a primary electrophysiological consequence of status epilepticus when progressive epileptogenesis occurs with max- imum of amplitude in the cellular layer. In areas outside of the generator of the BPS, this activity looks more like pathological high-frequency oscillations (pHFO), which were observed in ear- lier experiments. Key Words: Epileptogenesis—Pathological high-frequency oscillations—Bursts—Population spikes. The processes leading to recurrent spontaneous seizures after an initial precipitating event remain unclear. Hun- dreds of genes are up- or down-regulated after status epilepticus, resulting in changes in the properties of differ- ent receptors, channels, and transporters. Localization of specific patterns of electrical activity that could be markers of ongoing epileptogenesis and thereby predict recurrent seizure occurrence is one of the initial steps in identifying the molecular mechanisms of progressive epileptogenesis. In our earlier study (Bragin et al., 2004), we showed the appearance of high-frequency oscillations (HFOs) (80– 500 Hz) in the hippocampus ipsilateral to prior unilateral intrahippocampal kainic acid (KA) injection. There was a strong positive correlation between the occurrence and persistence of fast ripples (250–500 Hz) as well as patho- logical ripple frequency oscillations (80–200 Hz) in the dentate gyrus and the development of recurrent sponta- neous seizures. Address correspondence and reprint requests to Dr. A. Bragin at David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095, U.S.A. E-mail: abragin@ucla.edu doi: 10.1111/j.1528-1167.2007.01287.x In normal brain during immobility and slow wave sleep, ripples occur in the CA1 region of hippocampus (Buzsaki et al., 1992) and not in the dentate gyrus. We do not know, at this time, whether the same neuronal network generates normal ripples as well as pathological high-frequency os- cillations (pHFO) in both ripple frequency and fast ripple frequency, or whether they are generated by two or three different networks. To further study this question, we per- formed an analysis of voltage depth profiles of HFO at multiple recording sites after status epilepticus induced by unilateral intrahippocampal KA injection. METHODS Microelectrode implantation and recording Experiments were performed on eight adult Wistar rats (200–250 g) with implanted 16-channel recording probes across the right CA1-DG areas with coordinates AP = -3.5; L = 2.0; V = 4.5 for the deepest microelectrode. Probes consisted of sixteen 20-μm tungsten wires glued together, and cut so the distance between recording sites within each probe was 200 μm. Ground and indifferent 35