Abstracts

Rationale: Past studies that utilized the flurothyl model of seizure induction have demonstrated impairment of spatial learning and memory in both neonatal and adult rats. However, these studies focused on inducing several seizures and later examining the effects on learning and memory. The impact of a single acute seizure on learning and memory has not been investigated in mice. Methods: In this study, we placed an adult male 129SvEvTac mouse in an inhalation chamber. We then exposed the animal to the inhalant flurothyl (infusion rate of 50 µL/min) until a behavioral seizure (wild running with tonic-clonic seizure) was induced. We ran parallel control subjects in an inhalation chamber for the same time as the seizure mice. Either one hour or six hours later we examined associative learning and memory in delay fear conditioning. In delay fear conditioning the animal was first placed in a fear conditioning chamber. We then presented 20s of 80-dB white noise, which was immediately followed by a 0.7-mA footshock (unconditioned stimulus). We administered two presentations of the sound (conditioned stimulus) and shock pairings. We then examined the acquisition of the associative conditioning by testing the mice 24 hr post-seizure. During this testing period we made changes to the fear conditioning chamber to introduce a novel context. We then placed the mice in the testing chamber and measured their freezing behavior in the new context for 3 min. We also observed their freezing behavior when we presented the white noise for 3 min. This was the sound that was previously associated with shock. Results: We found that mice that had experienced a single seizure 1 hr prior to training on the previous day showed a significant impairment in associative conditioning to the conditioned stimulus compared to controls t(1,13) = 2.54, p < 0.05. However, the seizure mice were no different in their freezing behavior in the new context compared to controls t(1,13) = 1.6, p = 0.14. We ran a separate set of mice in the open field test to determine whether their activity levels changed after seizures. We wanted to eliminate the possibility that the decrease in freezing was due to hyperactivity. We did not find a difference in total activity in mice that had a single flurothyl seizure compared to control mice in the open field test 24 hr after a seizure t(1,13) = 0.24, p = 0.81. Mice that had experienced a seizure 6 hr prior to training did not show any significant difference in freezing behavior compared to controls 24 hr after a seizure when presented with the conditioned stimulus t(1,9) = 0.81, p = 0.44 or in the new context t(1,9) = 0.76, p = 0.67. Conclusions: These findings suggest that a single acute flurothyl seizure induced 1 hr but not 6 hr prior to associative learning impairs long term fear memory. In addition, the change in freezing behavior does not appear to be due to a change in activity levels. These findings have implications for understanding the acute effect of seizures on acquiring new knowledge.