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1 Comparative Medicine, Stanford University, Stanford, California, United States
2 Comparative Medicine and Neurology & Neurological Sciences, Stanford University, 94305, California, United States
* To whom correspondence should be addressed. E-mail: psb{at}stanford.edu.
Although much is known about persistent molecular, cellular, and circuit changes associated with temporal lobe epilepsy, mechanisms of seizure onset remain unclear. The dentate gyrus displays many persistent epilepsy-related abnormalities and is in the mesial temporal lobe where seizures initiate in patients. However, little is known about seizure-related activity of individual neurons in the dentate gyrus. We used tetrodes to record action potentials of multiple, single granule cells before and during spontaneous seizures in epileptic pilocarpine-treated rats. Subsets of granule cells displayed four distinct activity patterns: increased firing before seizure onset, decreased firing before seizure onset, increased firing only after seizure onset, and unchanged firing rates despite electrographic seizure activity in the immediate vicinity. No cells decreased firing rate immediately after seizure onset. During baseline periods between seizures, action potential waveforms and firing rates were similar among the four subsets of granule cells in epileptic rats and in granule cells of control rats. The mean normalized firing rate of granule cells whose firing rates increased prior to seizure onset deviated from baseline earliest, beginning four minutes before dentate gyrus electrographic seizure onset, and increased progressively, more than doubling by seizure onset. It is generally assumed that neuronal firing rates increase abruptly and synchronously only when electrographic seizures begin. However, these findings reveal heterogeneous and gradually building changes in activity of individual granule cells minutes before spontaneous seizures.
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