Spike-wave discharges are uncoupled with cognitive outcome in aged Long-Evans rats
Craig Myrum1,2, Zach Uttke3, Diba Ramezan4
1Laboratory of Behavioral Neuroscience, Neurocognitive Aging Section, National Institutes of Health (NIH), National Institute on Aging, Baltimore, MD, USA. cmyrum@loyola.edu.
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.
