Abstracts

The genetic absence epilepsy rats from Strasbourg (GAERS) model is a well established model of generalised epilepsy. Electrophysiological abnormalities that occur in GAERS have been described [italic]in vivo[/italic], but underlying ion channel and network activities are incompletely understood. The aim of this study was to determine whether specific thalamocortical oscillatory activity recorded in GAERS brain slices differs from non-epileptic controls (NEC). NEC or GAERS rats (12-14 weeks) were anesthetized with pentobarbitone, decapitated and the brain rapidly removed to perfusion with ACSF. Thalamacortical slices (300-450 micron) were cut in the axial plane. Bipolar electrodes were placed in the nucleus reticularis thalamus (nRt) and ventrobasal thalamus (VB) and nRt activity was evoked by electrical stimulation. In other experiments recording electrodes were used in both the neocortex and the VB. Spontaneous and electrically-induced activity were recorded, and effects of a non-selective K+-channel blocker, 4-aminopyridine (4-AP), and low Mg²⁺artificial cerebral spinal fluid (ACSF) were studied. 17 and 11 slices from 6 GAERS and 4 NEC, respectively, were studied. Spontaneous bursts of oscillatory activity were apparent in slices from the GAERS animals and these activities were at distinct frequencies of 1.7[plusmn]0.1 Hz, 2.7[plusmn]0.1 and 5.4[plusmn]0.3 Hz (n=4 for each). The duration of oscillatory bursts in these animals was averaged 12.9[plusmn]1.4 seconds (n=24 bursts calculated from 20 different traces). In the NEC animals only very brief, transient discharges with low frequency were seen. In GAERS, application of 4-AP evoked highly organised fast oscillatory bursts of electrical activity. Bursts of oscillatory activity could also be evoked in thalamocortical slices from GAERS by electrical stimulation of the nRt/VB boundary. In some recording sequences, coincident thalamocortical oscillations were obtained. Preliminary experiments have shown that calcium transients in the VB, measured using calcium ion-sensitive fluorescent probes, can be regulated by electrical stimulation of the nRt. Specific fast oscillatory activity was seen in thalamocortical slices from GAERS but not in NEC rats. Such aberrant activity could underly the seizures seen in this model. In future studies, optical imaging techniques will be used to characterize the ion channel activities associated with these GAERS-specific oscillations at both the cellular and network level. (Supported by NHMRC (Australia) and ARC (Australia))