Abstracts

Rationale: Recent reports have indicated that a single short seizure can impair the retention of learning in delay fear conditioning. However, it is not clear whether this impairment is limited to the amygdala, nor is it clear how long-lasting the memory impairment may be. The current study seeks to assess hippocampal-dependent memory impairment at 24 hr and 1 wk following an acute seizure in C57BL/6 mice to answer these questions. Methods: We placed 6 wk old male C57BL/6 mice (n = 8) into an inhalation chamber and infused flurothyl into the chamber until a generalized (tonic-clonic) seizure occurred. Control animals (n = 9) were run concurrently in a second inhalation chamber, but not exposed to flurothyl. An hour later mice were trained in trace fear conditioning. The mice were then tested 24 h and 1 wk later for cued recall. To assess changes to locomotor activity following a seizure, another cohort of mice (n = 7) was tested in a 10 min open field test 24 h and 1 wk after seizure induction. For comparison, sham controls animals (n = 7) were placed into an inhalation chamber, but not exposed to flurothyl prior to testing in the open field 24 h and 1 wk later. Results: A two-way ANOVA indicated a main effect of time for the 24-hour cued recall test F(12,180) = 4.25, p < .0001, however no significant difference between the control and seizure groups F(1,15) = 2.01, p > .05. The 1 week follow up test showed a significant main effect of group F(1,15) = 13.85, p < .01 and an effect of time F(12,180) = 3.02, p < .0001 indicating that there was a significant difference in memory retention at this time point. Results from the open field indicated a significant suppression of locomotor activity at 24 h t(1,12) = 2.6, p < .05, but not 1 wk t(1,12) = 0.1112, p > .05. We also found a similar difference in rearing frequency at 24 h U = 6.5, p < .05, but not at 1 wk U = 15.5, p > .05. There were no differences between groups in horizontal movement, time spent in the center versus surround, stereotypy, rearing duration, clockwise and counterclockwise revolutions, or number of fecal boli. Conclusions: There was significant impairment in cued recall 1 wk, but not 24 h following a seizure 1 h prior to trace fear conditioning. In addition, we ran open field to determine if changes in activity level were responsible for the results of trace fear conditioning. We found a transient suppression of activity level 24 h, but not 1 wk following a seizure. Together this data suggests that there may be a period after a seizure in which new learning can be retained, but that hippocampal-dependent memory may be impaired as time passes following the seizure. This data indicates a seizure alone in the absence of chronic changes to the brain can affect learning and memory for events occurring shortly afterward. Funding: NIH Grant R155088776