Development of Acoustic Priming‐Induced Abnormal Excitation in the Hippocampus of the Noda Epileptic Rat (NER)

Abstract

Purpose: The Noda epileptic rat (NER), which was found in a colony of Crj:Wistar rats, shows spontaneous tonicxlonic convulsions at a frequency of approximately once per 30 h. However, weekly applied acoustic priming consistently induces tonic‐clonic convulsion with sound stimuli. When NERs were given sound stimuli (95 dB, 8 kHz, 30 s) weekly from age 3 weeks, the percentage of animals with audiogenic seizures increased with age and was 100% after age 9 weeks. The audiogenic‐response score to quantify the intensity of seizure responses also increased with age. Frontal cortical and hippocampal electroencephalograms (EEGs) showed low‐voltage spike‐and‐wave complexes during tonic convulsions, which evolved into high‐amplitude spike‐ or polyspike‐and‐wave complexes during clonic convulsion. Immediately after cessation of the seizures, the EEG showed a flattening or diffuse slowing. To elucidate the development of the seizure induction by acoustic priming, we examined the epileptiform discharges in the in‐terictal EEG as a function of age. Methods: The acoustic priming was applied to NERs from age 7 to 35 weeks. Cortical and hippocampal EEGs were recorded weekly during the interictal stage for 15 min after a 15‐min habituation by using implanted electrodes. Results: Sporadic spikes were observed predominantly in the hippocampus with age, although they were rarely synchronized in the cortex. Hippocampal spikes were observed in two (33.3%) of six animals at age 7–10 weeks, 23 (82.4%) of 28 animals at age 11–15 weeks, 12 (85.7%) of 14 animals at age 16–19 weeks, and 21 (100%) of 21 animals at age >20 weeks. This development of abnormal hippocampal discharges with acoustic priming was in line with the development of convulsive seizures. Conclusions: Development of hippocampal excitation induced by acoustic priming is thought to lead to the induction of convulsive seizures in the NERs.