Contribution of GABAA and GABAB receptors to thalamic neuronal activity during spontaneous absence seizures in rats

Abstract

The contribution of GABAergic mechanisms in thalamic relay nuclei to spike and wave discharges (SWDs) during spontaneous seizures was assessed using the WAG/Rij strain of rats, an established genetic model of absence epilepsy, in combination with single-unit recordings and microiontophoretic techniques in the ventrobasal thalamic complex in vivo. Spontaneous SWDs occurring on the electroencephalogram at 5-9 Hz were associated with burst firing in thalamocortical neurons, which was phase-locked with the spike component. Microiontophoretic application of the GABAA receptor antagonist bicuculline significantly increased the magnitude of SWD-related firing in all tested cells. Application of the GABAB receptor antagonist CGP 55845A exerted a statistically insignificant modulatory effect on neuronal activity during spontaneous SWDs but significantly attenuated the bicuculline-evoked aggravation of SWD-related firing. The data indicate that, in thalamocortical neurons, (1) GABAA receptor-mediated events are recruited with each SWD, (2) SWD-related activity can be evoked with no significant contribution of GABAB receptors, and (3) blockade of GABAA receptors potentiates SWD-related activity, presumably through an indirect effect mediated through GABAB receptors. These results vote against a predominant or even exclusive contribution of GABAB receptors to spontaneous SWDs in thalamic relay nuclei in the WAG/Rij strain, but rather point to a critical role of GABAA receptor activation. This conclusion is in support of the view that the two subtypes of GABA receptors play a differential role in fast (5-10 Hz) and slow (3 Hz) spike-wave paroxysms observed during absence seizures.