Abstracts

Rationale: Fast ripples are transient EEG signals in the 200-600 Hz frequency band lasting less than 100 ms. These are found only in epileptic brain tissue. While fast ripples are considered to be a specific marker for the area of the brain in which seizures begin, their role in cognitive function of the brain is unclear. Here we studied the relationship of fast ripples with single cell firing patterns in epileptic rats. Hippocampal place cells fire selectively in specific and restricted locations (place fields) as rodents move through open environments. Hippocampal place cells "learn" to encode the salient features of experience through receptor-dependent synaptic plasticity mechanisms, and this rapid and persistent neuronal encoding is a crucial step toward the formation of long-term spatial memory. Place cells therefore serve as powerful surrogate markers for assessing spatial memory. Methods: We obtained extracellular recordings of place cells and interneurons using six tetrodes placed in the CA1 region of adult epileptic rats (n=8) and controls (n=9). EEG (filtered at 100-475 Hz) through eight electrodes was also recorded. The epileptic rats had undergone pilocarpine-induced status epilepticus and all had spontaneous recurrent seizures. Ictal and post-ictal EEG recordings were not assessed. Results: Place cell function was abnormal in the epileptic rats with reduced coherences, information content, firing rates, and larger field size compared to controls. Interneuron firing characteristics did not differ between the epileptic rats and controls. Fast ripples, occurring at a frequency of 200-300 Hz, were seen in all epileptic rats but none of the control rats. The asymmetry index, defined as the ratio of the mode of the interspike interval to the mean interspike interval, was significantly higher in epileptic rats during periods of ripples and interictal spikes (0.0048±0.0014) than in epileptic rats during epochs without ripples or interictal spikes (0.0029±0.0001), suggesting that ripples or interictal spikes enhanced variability of firing. Interneurons had lower asymmetry scores than controls, regardless of whether ripples were present or absent. Ripples were associated with synchronous firing of interneurons and reduction of place cell firing, followed rapidly by periods of increased place cell firings. Theta modulation of action potential firing was also impaired during periods of fast ripples. Conclusions: Our results demonstrated that fast ripples are present in brains of epileptic rats and occur at variable frequencies. Ripples are associated with an increase in the asymmetry of place cell, but not interneuron firing. In addition, fast ripples are associated with increased synchronous firing of interneurons and a transient decrease in place cell firing followed by increase firing. Taken together, our results show that fast ripples can alter the single firing characteristics of both place cells and interneurons. Fast ripples may serve not only as a marker of epileptogenesis, but cognitive impairment as well.