Is Spontaneous High-Voltage Rhythmic Spike Discharge in Long Evans Rats an Absence-Like Seizure Activity?

Abstract

Shaw, Fu-Zen. Is spontaneous high-voltage rhythmic spike discharge in Long Evans rats an absence-like seizure activity? J Neurophysiol 91: 63-77, 2004. First published June 25, 2003 10.1152/jn.00487.2003. 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.

The hippocampus participates in a pharmacological rat model of absence seizures

“…HVS activity in the neocortex of Long-Evan rats has long been known to be associated with vibrissal and facial muscle movements (Vanderwolf, 1975;Semba et al, 1980;Shaw, 2004). More recent studies indicated that HVS involved thalamocortical structures (Buzsaki, 1991;Kandel and Buzsáki, 1997), and was suppressed by anti-absence anticonvulsants, such as ethosuximide and valproate (Shaw, 2007), similar to SWDs in spontaneous genetic models of absence seizures (Coenen et al, 1992), or PDs induced by GBL (Snead et al, 1999).…”

“…In many rats, occasional, high-amplitude 6-9 Hz activity called high-voltage spindles (HVS) could appear in the neocortex and thalamus during baseline immobility ( Fig. 1A, B; Vanderwolf, 1975;Semba et al, 1980;Buzsáki, 1991;Shaw, 2004). An episode of HVS consisted of a burst of 6-9 Hz spike-and-wave discharges that waxed and waned over 1-4 s duration (Fig.…”

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

“…1b, d and f), amplitude 0.2-1.0/0.3-1.0/0.1-2.0 mV, duration 1-30/5-60/1-40 s (Akman et al, 2010;Coenen and Van Luijtelaar, 2003;Depaulis and Van Luijtelaar, 2005;Polack and Charpier, 2006;Shaw, 2004). The number of SWDs may vary between 15-40/20-80/6-90 (per hour) in WAG/Rij rats, GAERS rats and Long Evans rats depending on the time of the day and age of animals (Akman et al, 2010;Coenen and Van Luijtelaar, 2003;Depaulis and Van Luijtelaar, 2005;Polack and Charpier, 2006;Shaw, 2004). To avoid the modulatory effect of age and sleep-wake cycle on SWD number, electrophysiological recordings were carry out on eight months old animals (±1 week) between 4.00 PM and 8.00 PM.…”

“…injections were not included into the analysis. In relation to individually different SWD number and duration (Kovács et al, 2006;Polack and Charpier, 2006;Shaw, 2004), the changes in SWD numbers and duration were expressed in percentage of average control measures (three-day Table 1 The treatment protocol of the twelve animal groups carried out WAG/Rij rats, GAERS rats and Long Evans rats. Abbreviations: IND, indomethacin; i.p., intraperitoneal; LPS, lipopolysaccharide; PTC day, post-treatment control day.…”

“…However, the effects of LPS on absence epileptic activity in freely moving animals have not been investigated in genetically epileptic GAERS rats and Long Evans rats. It was recently demonstrated that Long Evans rats also produce SWDs similarly to WAG/Rij rats and GAERS rats (Depaulis and Van Luijtelaar, 2005;Huang et al, 2012;Polack and Charpier, 2006;Shaw, 2004Shaw, , 2007Shaw et al, 2009;Van Luijtelaar et al, 2011) allowing the investigation of SWDs in this strain as well. Therefore, to validate and extend our previous results, in which we demonstrated the LPS induced increase in absence epileptic seizures in WAG/Rij rats (Kovács et al, 2006) we injected two doses of LPS (50 g/kg and 350 g/kg i.p.)…”