Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 25, Issue 12, Pages 3667-3677Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1460-9568.2007.05598.x
Keywords
EEG; epilepsy; interneurons; place cells; seizures
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS044295, R01NS027984] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS27984, NS44295] Funding Source: Medline
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Patients with epilepsy are at substantial risk for memory impairment. Animal studies have paralleled these clinical observations, demonstrating impaired hippocampal function as measured by spatial memory in rodents subjected to seizures. However, the mechanism of seizure-induced hippocampal impairment is unclear. Here we investigated the effects of recurrent seizures on water-maze performance, a behavioural measure of learning and memory, long-term potentiation (LTP; considered a test of synaptic plasticity and memory) and place-cell firing patterns, a single-cell indicator of spatial memory. LTP and CA1 place-cell activity were examined in separate groups of freely moving rats, before and after 10 flurothyl-induced seizures. Water maze performance was examined in a third group of rats, five with previously induced seizures and five controls. Recurrent flurothyl seizures were associated with marked impairment in LTP and a reduction in the frequency of the peak theta power. Compared to baseline recordings, place-cell firing patterns following recurrent seizures were significantly less precise, had lower firing rates and were less stable. Impaired place-cell firing was seen as early as after two seizures and persisted at least 72 h after the last seizure. Water-maze performance was also significantly impaired in animals that underwent recurrent seizures. No cell loss or synaptic reorganization was observed in the hippocampus or in several other cortical areas that are vulnerable to seizures. These results demonstrate that relatively brief excitatory events, not producing visible cell damage, can nevertheless cause long-lasting changes in hippocampal physiology, observable as impairments in place-cell function, LTP and spatial memory.
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