Altered Phase Precession and Compression of Temporal Sequences by Place Cells in Epileptic Rats

In the hippocampus, pyramidal cells encode information in two major ways: rate coding and temporal coding. Rate coding, in which information is coded through firing frequency, is exemplarily illustrated by place cells, characterized by their location-specific firing. In addition, the precise temporal organization of firing of multiple place cells provides information, in a compressed time window, about the temporal sequence of the locations visited by the animal. This encoding is accomplished through phase precession, a phenomenon whereby unit firing is linked to theta rhythm, one of the major hippocampal EEG oscillations. Although it is likely that this type of processing is critical for normal brain function, its involvement in pathologies associated with cognitive disorders is unknown. In this experiment, we determined whether the temporal organization of place cell firing is affected in an animal model of mesial temporal lobe epilepsy (MTLE), a disease accompanied with cognitive impairment. We investigated hippocampal coding and its relationship to theta rhythm in rats after status epilepticus (SE), a condition that leads to MTLE. We found a great proportion of SE place cells had aberrant phase/precession pattern and temporal organization of firing among pairs of neurons, which constitutes the compression of temporal sequences, was altered in SE rats. The same animals were also markedly impaired in the water maze task, a measure of spatial memory. We propose that the synaptic and cellular alterations observed in MTLE induce aberrant temporal coding in the hippocampus, contributing in turn to cognitive dysfunction.