Abstracts

Rationale: In the United States more than 2.9 million people are afflicted with epilepsy or seizure disorder. Temporal lobe epilepsy (TLE) remains the most prevalent classification of partial epilepsy and is associated with persistent deficits in cognition. Hippocampal network dysfunction and a reduction in theta oscillations are correlated with diminished spatial learning. We previously established that pilocarpine-induced epilepsy reduces hippocampal theta oscillations in freely moving rats and also impairs learning in the Barnes Maze. In the following experiment we demonstrate changes in hippocampal, medial septal (MSN), and anterior cingulate (ACC) theta oscillations in pilocarpine-treated epileptic animals behaving in a spatial recognition memory task.Methods: Rats were injected with 1 mg/kg scopolamine methyl nitrate followed 30 minutes later by 350 mg/kg pilocarpine. Convulsive seizures were terminated with 8mg/kg of diazepam after 240 minutes. Control rats received equivalent volumes of saline. On post injection date (PID) 28, single monopolar electrodes were stereotactically implanted in the MSN, right ACC and right hippocampus for EEG recording. Starting on PID 35 animals were habituated to an empty Plexiglass box for 10 minutes on consecutive days. On PID 37 animals were placed in the same box with spatial cues and two objects diagonally spaced 34 inches apart. Animals were allowed to explore the box for 15 minutes and were subsequently placed in a neutral cage for five minutes to rest. Animals were then placed back into the box for an additional five minutes with the objects positioned closer together (13 inches apart). Time locked EEG and video were continuously recorded during both habituation and testing phases. Custom Matlab script (P_episode) was used to determine percent time oscillating in theta (6-10 Hz).Results: In the spatial recognition task, pilocarpine-treated animals spent less time exploring the objects in both the distal and proximal configurations compared to controls. They also traveled a shorter total distance across all trials. Analysis of EEG revealed a reduction in theta oscillations in epileptic animals as compared to controls in both habituation and test trials. There was a specific reduction in theta during object interaction. These reductions were consistent across all recorded brain regions (hippocampus, MSN, ACC).Conclusions: The current findings demonstrate alterations in theta rhythmicity in multiple anatomical regions including hippocampus, MSN, and ACC in pilocarpine-treated epileptic animals. These data corroborate previous work by demonstrating spatial navigation deficits in epileptic animals while also exhibiting novel multi-nodal changes in theta oscillations during spatial recognition and object interaction. Ultimately, understanding the effects of epilepsy across the learning and memory circuit will enhance our ability to design and test therapeutic interventions to improve cognitive function and eliminate seizures in TLE patients.