Abstracts

Rationale: Early life seizures (ELS) in neonates cause long-term cellular changes in the brain, and carry cognitive consequences later in life. ELS cause long-lasting alterations in inhibitory transmission, which drive neuronal oscillations (EEG rhythms) that are important for cognitive processes. We propose that one of the mechanisms by which ELS induce cognitive impairments is through a disruption of neuronal oscillations. We simultaneously recorded theta (4-12Hz) and gamma (30-100Hz) oscillations in the hippocampus (both CA3 and CA1) and in the prefrontal cortex (PFC) in adult ELS rats performing a memory task called delayed-non-match-to-sample (DNMS). We hypothesized that decreased performance would be associated with alterations of oscillation amplitude and synchrony within and across structures. Methods: Five control rats and three ELS rats (exposed to 100 flurothyl seizures from days P15-30) were trained on the DNMS task in adulthood (P55-100). This short-term memory task involves both hippocampal and prefrontal structures. Local field potentials were recorded in vivo during all training sessions with depth electrodes in CA3, CA1, and PFC. Power and coherence were calculated dynamically with sliding windows (1s for theta; 0.2s for gamma) using Fourier analysis. Logistic regression and ANOVA statistics were used to compare power and coherence relative to performance. Results: Among 8 rats, 7926 trials were analyzed. ELS rats took significantly longer to learn the DNMS task (p<0.05), but eventually reached control performance levels as training progressed. ELS rats had a striking 30% increase in PFC theta power over controls during the trials (but not between trials), and this increase was significantly more prominent in correct trials. Correct trials were also accompanied by elevated CA3, and decreased PFC, gamma power in ELS rats. In addition, their CA1/PFC theta coherence was higher during the memory encoding period (p<0.001), but was not predictive of performance. Finally CA3/CA1 gamma coherence during retrieval was predictive of errors in all rats (p<0.001).