On the putative contribution of GABA(B) receptors to the electrical events occurring during spontaneous spike and wave discharges

Abstract

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of -68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that there are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA(B) IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.