Removing entorhinal cortex input to the dentate gyrus does not impede low frequency oscillations, an EEG-biomarker of hippocampal epileptogenesis

Abstract

Following prolonged perforant pathway stimulation (PPS) in rats, a seizure-free "latent period" is observed that lasts around 3 weeks. During this time, aberrant neuronal activity occurs, which has been hypothesized to contribute to the generation of an "epileptic" network. This study was designed to 1) examine the pathological network activity that occurs in the dentate gyrus during the latent period, and 2) determine whether suppressing this activity by removing the main input to the dentate gyrus could stop or prolong epileptogenesis. Immediately following PPS, continuous video-EEG monitoring was used to record spontaneous neuronal activity and detect seizures. During the latent period, low frequency oscillations (LFOs), occurring at a rate of approximately 1 Hz, were detected in the dentate gyrus of all rats that developed epilepsy. LFO incidence was apparently random, but often decreased in the hour preceding a spontaneous seizure. Bilateral transection of the perforant pathway did not impact the incidence of hippocampal LFOs, the latency to epilepsy, or hippocampal neuropathology. Our main findings are: 1) LFOs are a reliable biomarker of hippocampal epileptogenesis, and 2) removing entorhinal cortex input to the hippocampus neither reduces the occurrence of LFOs nor has a demonstrable antiepileptogenic effect.