Abstracts

Rationale: Comorbid memory impairments are common in patients with epilepsy. Memory impairments are worse with greater seizure frequency and severity. Recent reports have found that a single brief seizure impairs retention in contextual and delay fear conditioning. However, the question remains as to how long a single seizure can influence memory and which types of memory it can impair. To address these questions, we assessed trace fear memory at 1 wk and 2 wk after a seizure. We also tested recognition memory using the novel object recognition (NOR) task. Methods: We placed 6 wk old male C57BL/6 mice into an inhalation chamber and infused flurothyl until a generalized (tonic-clonic) seizure occurred. For comparison, we used control animals not exposed to flurothyl. Beginning 1 h later, we trained the mice in either trace fear conditioning (N = 20) or NOR. For trace fear conditioning, we tested cued recall at 1 wk and 2 wk post-seizure. For NOR we tested animals at either 24 h (N = 18) or 1 wk (N = 14) post-seizure by replacing one of the two familiar objects with a novel object and measuring investigation of the objects. Results: We found trace memory for the tone-shock association was impaired at 1 wk in mice that experienced a seizure prior to fear conditioning training. A two-way mixed ANOVA of freezing behavior at 1 wk indicated significant effects of time F(12, 216) = 8.54, p < 0.0001, group F(1, 18) = 8.51, p < 0.01, and a time x group interaction F(12, 216) = 3.15, p < 0.001. Similar results were found for cued recall at 2 wk for time F(12, 216) = 6.23, p < 0.0001, and group F(1, 18) = 8.87, p < 0.01. We trained mice in NOR following a seizure and found an overall decrease in time spent investigating each of the two identical objects F(3, 56) = 7.06, p < 0.001, but no difference among the durations investigating two objects for any groups F(1, 56) = 0.30, p > 0.05 were found. During the testing phase of NOR at 24 h, mice showed a preference for the novel object over the familiar object F(1, 32) = 8.28, p < 0.01, but there was no difference between control and seizure groups F(1, 32) = 0.77, p > 0.05. The mice tested at 1 wk all showed a preference for the novel object F(1, 24) = 10.49, p < 0.01, but there was no difference between control and seizure groups F(1, 24) = 0.92, p > 0.05. Conclusions: There was significant impairment in hippocampal-dependent trace fear conditioning 1 wk, and 2 wk following a seizure occurring 1 h prior to fear conditioning. In NOR, we found no impairment in recognition memory at either 24 h or 1 wk later. Together this data suggests that there is a selective effect of a single brief seizure on hippocampal-dependent trace memory versus recognition memory. Additionally the trace fear data indicates that impairments in memory detected at earlier time points do not recover with more time after a seizure. Funding: This research was funded by NIH NS056664 to JNL