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

Cortical and thalamic neurones play a major role in the generation/expressi on of spike and wave discharges (SWDs), the main electroencephalographic (E EG) feature of absence seizures. The detailed mechanisms leading to this pa roxysmal EEG activity, however, are still poorly understood. We have now ma de in vivo intracellular recordings from layer V cortical neurones of the f acial motor cortex and from thalamocortical (TC) neurones of the ventropost eromedial and ventroposterolateral nuclei in a well established model of th is 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 potent ials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic se quences were superimposed on a small tonic hyperpolarization that lasted fo r the whole duration of the SWD and was still present at potentials close t o -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential o f -68 mV, and always appeared as depolarizing events when recording with KC l-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lastin g IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, r espectively. The main feature of the intracellular activity recorded in cor tical neurones during spontaneous SWDs was the presence of rhythmic depolar izations. Their frequency was similar to the one of SWDs in the EEG, and wa s not affected by DC injection. The amplitude of the rhythmic depolarizatio ns, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neu rones was observed during SWDs compared to the inter-SWDs periods. Low freq uency electrical stimulation of the contralateral striatum evoked in cortic al neurones a short and a long lasting IPSP, whose waveforms were reminisce nt of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that th ere are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAER S TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimpose d 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 neurone s during spontaneous SWDs in GAERS. (C) 1999 Elsevier Science Ltd. All righ ts reserved.