Abstracts

Rationale: For the past several years, we have characterized Seizure- induced Sprouting in limbic pathways of young and adult experimental rat models of temporal lobe epilepsy. Our studies have shown that Seizure-induced Sprouting results in the progressive and permanent development of aberrant connections between hippocampal lamellas during the latent period preceding the occurrence of spontaneous seizures of increasing frequency. Our studies have focused upon reorganization of the CA1 pyramidal projection to the subiculum and collateral projections to neighboring CA1 pyramidal neurons in lamellas above and below the normal projection pattern, translamellar sprouting. We investigated the physiological consequences of this aberrant hippocampal circuitry reorganization. Methods: In-vivo evoked field potentials in Subiculum (fixed location) were recorded after stimulation in CA1 by an advancing electrode at multiple dorsoventral (DV) depths in saline-treated controls (n=3) and Kainic Acid (KA) treated male SD rats at 6-28 days (n=6; latent KA group) and >60 days (n=4; chronic KA group) after KA induced status epilepticus (KA-SE). fEPSPs were obtained under urethane using tungsten recording electrodes (0.5M?) and Platinum-Iridium bipolar stimulating (intertip distance 0.5mm) electrodes. 0.5ms square wave pulses of 1V at 2Hz evoked fEPSPs in Subiculum that were averaged for 10 events at each depth. Stimulation electrode was advance every 100?m along DV axis of CA1. For statistical and data analysis, we used Clampfit 10.2.Results: The DV extent of CA1 stimulation that evoked fEPSP in Subiculum was 3.6 0.23 mm in controls, 5.1 0.34 mm in latent KA group, and 6.2 1 in chronic KA group (control vs. latent and chronic KA groups were p=0.012 and p=0.045 respectively). The DV extent between latent and chronic KA groups was not different (p=0.14). Evoked fEPSPs in Subiculum consisted of components that evolve in morphology at different depths of CA1 stimulation. There was no difference in the amplitude, but progressive alterations in the area under the curve of fEPSPs in KA groups as compared to controls. Maximum amplitude values were -37.09 12.2 mV for control, -25.70 3.7 mV and -25.20 10.2 mV for latent and chronic KA groups (p=0.14 and 0.24 compared to controls). In contrast, the area under the curve for control group was significantly different to the chronic KA group, but not to latent KA rats. The areas were -416.4 174.7 mV*ms, -480.4 148.2 mV*ms and -1156 145.6 mV*ms for control, latent KA and chronic KA respectively (p=0.4 control/latent KA; p=0.01 control/chronic KA; p=0.007 between latent/chronic KA). Conclusions: Progressive physiological alterations in the recruitment of hippocampal lamellas during epileptogenesis were demonstrated after Kainic acid induced status epilepticus that parellel the development of aberrant translamellar sprouting and precede the later development of chronic spontaneous seizures. Funding: VA Merit Award to JEC