Related Experiment Video
Updated: Jun 23, 2026
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Effect of age on cognitive sequelae following early life seizures in rats
Havisha B Karnam1, Qian Zhao, Tatiana Shatskikh
1Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, New Hampshire 03756, United States.
Insights
Recurrent seizures in developing rats impair learning, memory, and activity, affecting synaptic function. The age of seizure onset did not significantly alter these long-term cognitive outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Cognitive Science
Background:
- Clinical studies suggest neonatal seizures are more detrimental than later seizures.
- Interpreting human studies is challenging due to varying causes of seizures across age groups.
- Animal models offer a controlled method to investigate age-dependent seizure effects on cognition.
Purpose of the Study:
- To determine if the age of seizure onset influences long-term cognitive deficits.
- To evaluate the impact of early-life recurrent seizures on adult behavior and synaptic function.
Main Methods:
- Rats experienced 50 seizures during early (postnatal days 0-10) or later (postnatal days 15-25) developmental periods.
- Adult rats were assessed using the Morris water maze, radial-arm water maze, open field, and active avoidance tests.
- Synaptic function was evaluated via long-term potentiation (LTP) and paired-pulse facilitation/inhibition.
Main Results:
- Both seizure groups exhibited impaired spatial memory and altered open field activity compared to controls.
- Recurrent seizures led to deficits in long-term potentiation (LTP), indicating impaired synaptic plasticity.
- No significant differences in active avoidance or paired-pulse inhibition were observed between groups.
Conclusions:
- Early-life recurrent seizures induce lasting deficits in learning, memory, and activity levels.
- Impaired synaptic efficiency (LTP) is a key consequence of developmental seizures.
- The age of seizure onset was not a critical determinant of the severity of long-term cognitive impairment.
Purpose:
Clinical studies have suggested that seizures in newborns are more damaging than seizures occurring in older children. However, these studies are difficult to interpret for a variety of factors including differing etiologies of seizures across ages. Animal studies can provide insights into the question of whether age of seizure onset in children is a factor in cognitive outcome.
Methods:
To evaluate the effect of age on seizure-induced cognitive impairment we subjected rats to 50 seizures from postnatal days P0-P10 or P15-P25. As adults the rats were studied in the Morris water maze, radial-arm water maze, open field, and active avoidance. To assess synaptic strength and network excitatory and inhibitory function animals were evaluated with long-term potentiation (LTP) and paired-pulse facilitation/inhibition.
Results:
Compared to controls, both groups of rats with recurrent seizures were impaired in spatial memory in both water maze tests, had altered activity in the open field, and did not differ from controls in active avoidance. Rats with recurrent seizures had impaired LTP but showed no deficits in paired-pulse facilitation or inhibition. While rats with later onset showed a trend to worse performance than rats with earlier seizures, the differences were not substantial.
Conclusions:
Recurrent seizures during development are associated with long-term behavioral deficits in learning, memory and activity level as well as impaired synaptic efficiency. Age of seizure onset was not a strong predictor of outcome.
