Abstracts

Rationale: CA1 pyramidal cells comprise one of the principal projection neurons of hippocampus. Previous studies have shown that the firing rates of a subset of hippocampal granule cells and CA3 pyramidal cells increase prior to seizure onset, possibly as part of a preictal “wind-up”. We hypothesized that CA1 pyramidal cells participate in this preictal buildup to seizures, thus projecting seizure-related changes in firing rate observed in upstream structures. Methods: Multiple, single neurons were recorded from CA1 in epileptic, pilocarpine-treated rats at least 4 months following pilocarpine-induced status epilepticus. Broadband, tetrode recordings were made before, during and after spontaneous seizures in awake, freely-moving rats. Seizure onset was determined electrographically by the paroxysmal onset of rhythmic fEPSPs from an electrode placed in the hilus to allow timing comparisons to previous recordings obtained from dentate gyrus and CA3. Multiple, single neurons were isolated offline by digital filtering, threshold detection and cluster cutting. Neurons were identified as pyramidal cells or interneurons based on spike-width, firing rate and inter-spike-interval distribution. Results: Twenty spontaneous seizures preceded by an inter-ictal period lasting at least 1 hr were recorded from 4 rats (5 seizures per rat). Preliminary results from the first seizure from each rat isolated 101 neurons. 75 neurons met the criteria of pyramidal cells, 21 neurons met the criteria of interneurons and 5 neurons that did not match either category were dropped from analysis. Compared to firing rates during a baseline period -40 to -20 min prior to seizure onset, the firing rates of 5 pyramidal cells (6.7%) increased in the minute prior to seizure onset, the rates of 6 cells (7.5%) decreased, and those of 8 (10.7%) increased following seizure onset (p<.05, t-test). Changes in interneuron firing rate were not examined for this abstract. The mean firing rate across the population of all pyramidal cells did not change prior to, but did increase following seizure onset (p=.0011, repeated-measures ANOVA, Bonferroni correction). Conclusions: Preliminary findings in this study show that firing rates of 6.7% of CA1 pyramidal cells increased beginning 1 min prior to seizure onset. Our previous results show that the mean firing rates of 33.6% of granule cells increased beginning 4 min prior to seizure onset, while those of 41.7% of CA3 pyramidal cells increased beginning 2 min prior to seizure onset. This suggests that CA1 pyramidal cells do not participate in a preictal, or “windup”, period. The mean firing rate across the population of CA1 pyramidal cells, however, does increase following seizure onset. This leads to a working hypothesis that CA1 acts as the final “tumbler” in the hippocampal seizure “lock”; i.e., CA1 pyramidal cells may initially resist seizure-related activity in CA3, but are eventually activated by it, allowing or possibly contributing to the locally recorded electrographic seizure onset. This work was supported by NIH/NINDS.