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Rational <p>Rodent EEGs display 7–12&#xa0;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.</p> Objective <p>To test whether SWD activity contributes to the memory decline reported in aged rats.</p> Methods <p>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&#xa0;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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Craig Myrum,
  • Zach Uttke,
  • Diba Ramezan,
  • Margaret E Stelzner,
  • Jeffrey M. Long,
  • Peter R. Rapp

摘要

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.