Kainic acid-induced status epilepticus results in anterograde amnesia for contextual learning.

Individuals with epilepsy suffer a decrease in quality-of-life, and a major factor in this decrease is memory deficits. One of the most common memory deficits those with epilepsy report is a brief period of amnesia surrounding a seizure event. Recent evidence indicates a single acute seizure disrupts learning which occurs within one-hour but not six-hours post-seizure. In this study, we examined if a kainic acid (KA) induced episode of status epilepticus (SE) will disrupt memory for an associative memory task occurring one (1hr) or six hours (6hrs) post-SE recovery. Recall tests for contextual and cued fear memory were run 24hrs and 1wk after SE induction using Delay Fear Conditioning (DFC). We also collected hippocampal tissue from a separate cohort of mice at 24hrs and 1wk to examine histological alterations which may be associated with memory recall deficits. We observed contextual, but not cued, fear memory deficits at both 24hrs and 1wk recall for males and females trained 1hr after SE. When trained 6hrs after SE contextual memory recall was impaired at 24hrs but not 1wk later in males and females. We conducted western blot analysis for factors associated with decreased memory recall such as increased immune response (IBA1), astrocyte reactivity (GFAP), and mTOR hyperactivity (AKT/pAKT and S6/pS6). We observed an increase in IBA1 levels at 24hrs and 1wk, increases in AKT and pAKT at 24hrs, and pS6 at 24hrs for KA mice. This study suggests a single SE episode can disrupt contextual memory for up to six hours after SE cessation and altered PI3K/AKT/mTOR signaling and inflammation may play a role in post-seizure memory disruption.