Abstracts

To assess how cognitive processes underlying learning and memory are affected in epilepsy, we previously studied hippocampal place cell activity in the pilocarpine rat model. Place cells are hippocampal pyramidal cells that fire when the animal enters a particular location in the environment called the cell[apos]s place field. Since place cells have different fields for different environments, it is believed that they reflect the rat[apos]s memory of its spatial location. Our previous study showed that place cell signal and field stability were adversely affected in epileptic rats. To continue the investigation of epilepsy-related cognitive disorders, we studied another important aspect of hippocampal neuronal activity: the neuronal firing relationship to hippocampal theta rhythm. When a rat enters a field, place cells fire generally on the peak of CA1 theta waves. As the rat crosses the field, the cells tend to fire earlier on successive theta cycles. This phenomenon, called phase precession, a form of temporal coding, is also believed to play a crucial role in learning and memory processes. We hypothesize that this phenomenon is also affected in epileptic rats., Control rats (N=5) and lithium-pilocarpine rats (N=6) were used. All rats were trained to alternate between the extremities of a linear track for a food reward. They were implanted with a microelectrode array that allowed independent manipulation of 6 tetrodes (bundles of four 30[mu]m nichrome wires for unit recording) and two 100[mu]m electrodes for EEG. Unit electrodes were aimed to the CA1 layer of the right dorsal hippocampus. EEG recordings consisted in bipolar differential recordings across the CA1 cell layer. EEG were filtered in the theta band (6-12 Hz) and, for each pyramidal cell displaying a field in the middle part of the track, it[apos]s firing relationship to the phase of the theta rhythm was analyzed., We found that phase precession, i.e. the circular-linear correlation between theta phase and the firing of the cells, while the rat entered the field was altered in epileptic rats as compared to untreated animals.
Almost half of the selected place cells (48%), i.e. cells that had a field in the middle of the track, didn[apos]t show a correlation between theta phase and the animal[apos]s distance in the field.
In most of the other cases, the correlation, although significant, is weak (mean r = -0.153). For the whole population of selected cells in the SE group (N= 52), the average correlation is smaller than in untreated animals (r = -0.153 vs r = -0.467)., These results show that the temporal coding, as well as the rate coding, are affected in epilepsy. Such an abnormality likely contributes to the cognitive disorders observed in patients with epilepsy., (Supported by Western Massachusetts Epilepsy Awareness Fund, Friends of Shannon McDermott, Sara Fund, and NINDS (Grants: NS27984 and NS44295).)