Abstracts

Rationale: The dentate gyrus is thought to play a key role in limiting seizure propagation into the hippocampus. However alterations in other hippocampal networks that affect activity patterns or synchrony may also contribute to seizure generation. We simultaneously documented the spatial and temporal relationships of abnormal electrical oscillations in the cortico-hippocampal network to examine this idea. Methods: Extracellular field potentials were recorded for 2 hr using a multi-electrode array of 60 electrodes spaced at 500um intervals in acute entorhino-hippocampal slices isolated from control or pilocarpine-treated epileptic rats. Network activity was induced with low Mg2+ buffer or by addition of bicuculline (BMI) and elevated K+. Fast Fourier Transform was used to detect slow oscillations (10-100Hz; SO), ripples (100-200Hz; RP) and fast ripples (201-1000 Hz; FR).Results: Combined frequency spectra showed the presence of SO in controls and the appearance of distinct peaks in RP and FR ranges in slices from epileptic rats in both low Mg2+ and BMI. Temporal and spatial analyses of frequency spectra showed a significant increase in SO rates in response to low Mg2+ in all hippocampal regions except CA3c in epileptic compared to control. In epileptic hippocampus RP and FR rates also increased in low Mg2+, most prominently in CA3b. In BMI, SO increased most prominently in dentate gyrus (DG) and CA3; RP and FR rates were variable across slices. Synchrony as judged by autocorrelations in controls was highest in CA3b,c and hilus for low Mg2+ and in CA3b for BMI in all 3 frequency ranges. Epileptic hippocampus showed increased autocorrelations in DG, hilus and CA3b for low Mg2+ but little change for BMI. Covariance of oscillations between different hippocampal subregions in control was highest between CA3 subregions in all frequency ranges for low Mg2+ and between DG, hilus and CA3b for SO in BMI. In epileptic hippocampus covariances increased between DG, hilus and CA3b for all frequency ranges in low Mg2+ but decreased between DG, hilus and CA3 and within CA3 for BMI. Conclusions: These data show that synchrony and/or frequency spectra are modulated by epileptogenesis in most regions of the hippocampal formation. Analyses of the temporal and spatial relationship between different frequency oscillations and interictal spikes and seizures are underway. Supported by CDMRP grant PR030035(SB) and EFA Postdoctoral Fellowship (BG).