Abstract
Low-voltage fast (LVF)- and hypersynchronous (HYP)-seizure onset patterns can be recognized in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80-200 Hz) and fast ripples (250-500 Hz) have been linked to each pattern, with ripples predominating during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the contribution of neural networks with distinct transmitter signaling characteristics. Here, we tested this hypothesis by analyzing the seizure activity induced with the K(+) channel blocker 4-aminopyridine (4AP, 4-5 mg/kg ip), which enhances both glutamatergic and GABAergic transmission, or the GABAA receptor antagonist picrotoxin (3-5 mg/kg ip); rats were implanted with electrodes in the hippocampus, the entorhinal cortex, and the subiculum. We found that LVF onset occurred in 82% of 4AP-induced seizures whereas seizures after picrotoxin were always HYP. In addition, high-frequency oscillation analysis revealed that 4AP-induced LVF seizures were associated with higher ripple rates compared with fast ripples (P < 0.05), whereas picrotoxin-induced seizures contained higher rates of fast ripples compared with ripples (P < 0.05). These results support the hypothesis that two distinct patterns of seizure onset result from different pathophysiological mechanisms.