Is spontaneous high-voltage rhythmic spike discharge in Long Evans rats an absence-like seizure activity?

Abstract

A distinct high-voltage rhythmic spike (HVRS) discharge characterized by a barrage of negative spikes oscillating at 5-12 Hz was observed in chronically implanted Long Evans rats. Spontaneous HVRS discharges were exhibited in 90% of 40 Long Evans rats and occurred during sudden arrest of ongoing behavior (immobility) with occasional facial/whisker twitching. However, the function of HVRS discharges in Long Evans rats remains inconclusive to date and has been associated with alpha tremor/mu rhythm, attentive mu wave, and absence seizure. To elucidate the function of HVRS discharges in Long Evans rats, several experiments were performed. In a 6-h recording session (12:00-18:00), HVRS activities primarily occurred in several specific vigilance states, being particularly abundant in a short-lasting period before vigilance changes. Several characteristics, such as durations, oscillatory frequencies, and interspike intervals (ISIs) of HVRS discharges, were altered during wake-sleep states. Oscillatory frequencies were negatively correlated with durations of HVRS segments. In addition, ISIs of a HVRS episode exhibited a crescendo-decrescendo pattern. These variable ISIs could explain why a negative correlation was found between oscillatory frequencies and durations of HVRS episodes. Moreover, HVRS discharges were demonstrated to have widespread and near-synchronous distribution to bilateral cortical areas. In addition, innocuous electrical stimuli were unable to stop ongoing HVRS discharges. By contrast, noxious stimuli elicited behavioral arousal and immediately terminated most HVRS discharges. Cortical-evoked potentials in response to mild electrical stimulation under HVRS discharges were different from those under waking state but resemble those under slow-wave sleep with a smaller magnitude. Moreover, the temporal and spectral characteristics of spontaneous HVRS activities were analogous to those of seizure activities induced by penicillin and pentylenetetrazol. The incidence of spontaneous HVRS discharges was significantly decreased by ethosuximide administration. Based on these results, HVRS discharge might not be associated with a voluntary mu-rhythm behavior, instead it behaves as an absence-like seizure activity. These results were also collaborated using other genetic absence-seizure rats, such as WAG/Rij and GAERS rats. Possible mechanisms for the generation and termination of paroxysmal HVRS discharges are also discussed.