Region-specific Effects of Early-life Status Epilepticus on the Adult Hippocampal CA3 – Medial Entorhinal Cortex Circuitry In vitro: Focus on Interictal Spikes and Concurrent High-frequency Oscillations

Abstract

Convulsive status epilepticus (SE) in immature life is often associated with lasting neurobiological changes. We provoked SE by pentylenetetrazole in postnatal day 20 rat pups and examined communication modalities between the temporal hippocampus and medial entorhinal cortex (mEC) in vitro. After a minimum of 40 days post-SE, we prepared combined temporal hippocampal – medial entorhinal cortex (mEC) slices from conditioned (SE) and naïve (N) adult rats and recorded 4-aminopyridine-induced spontaneous epileptiform interictal-like discharges (IED) simultaneously from CA3 and mEC layer V-VI. We analyzed IED frequency and high frequency oscillations (HFOs) in intact slices and after surgical separation of hippocampus from mEC, by two successive incisions (Schaffer collateral cut, Parasubiculum cut). In all slices, IED frequency was higher in CA3 vs mEC (5N, 4SE) and Raster plots indicated no temporal coincidence between them either in intact or in CA1-cut slices (4N, 4SE). IED frequency was significantly higher in SE mEC, but similar in SE and N CA3, independently of connectivity state. Ripples (R) and Fast Ripples (FR) coincided with IEDs and their power differed between SE and N intact slices (22N, 12SE), both in CA3 and mEC. CA3 FR/R ratios were higher in the absence of mEC (14N, 8SE). Moreover, SE (vs N) slices showed significantly higher FR/R ratios independently of the presence of mEC. Taken together, these findings suggest lasting effects of immature SE in network dynamics governing hippocampal-entorhinal communication which may impact adult cognitive, behavioral, and/or seizure threshold sequalae.