Spike-wave discharges are uncoupled with cognitive outcome in aged Long-Evans rats

Abstract

Abstract Rational Rodent EEGs display 7–12 Hz oscillations called spike-wave discharges (SWDs) that are more abundant with age, and some data suggest that they might interfere with hippocampus-dependent memory processing. Objective To test whether SWD activity contributes to the memory decline reported in aged rats. Methods Spatial learning was assessed in young and aged Long-Evans (LE) rats using a water maze protocol where aged rats display substantial interindividual variability in hippocampus-dependent memory. We then collected 24 h EEG data to quantify SWD incidence and duration among young and aged animals. Lastly, we took a pharmacological approach to test the efficacy of two antiepileptic drugs—levetiracetam and ethosuximide—at reducing SWD activity. Results We found that SWDs were significantly more frequent in aged rats than young, but entirely unrelated to between-subject differences in cognitive outcome. Age-dependent increases in SWD frequency were also insensitive to levetiracetam at doses known to reverse memory impairment in aged rats, but potently inhibited by the other antiepileptic drug, ethosuximide, that functions through a different mechanism of action. Conclusion Together these findings provide evidence that the disrupted excitatory/inhibitory balance associated with individual differences in cognitive aging is unrelated to the SWD increase seen in aged rats.

Affiliated Institutions

• National Institute on Aging US
• Loyola University Maryland US
• National Institutes of Health US

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