title: Contribution of GABA(A) and GABA(B) 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 GABA(A) receptor antagonist bicuculline significantly increased the magnitude of SWD-related firing in all tested cells. Application of the GABA(B) 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) GABA(A) receptor-mediated events are recruited with each SWD, (2) SWD-related activity can be evoked with no significant contribution of GABA(B) receptors, and (3) blockade of GABA(A) receptors potentiates SWD-related activity, presumably through an indirect effect mediated through GABA(B) receptors. These results vote against a predominant or even exclusive contribution of GABA(B) receptors to spontaneous SWDs in thalamic relay nuclei in the WAG/Rij strain, but rather point to a critical role of GABA(A) 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.
authors.affiliation: Institute of Physiology, Medical School, Otto-von-Guericke University, 39120 Magdeburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Staak
authors.forename: H C
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000196:embryology* / Q000378:metabolism* / Q000503:physiopathology; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007478:Iontophoresis; D016014:Linear Models; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010721:Phosphinic Acids / Q000008:administration & dosage; D011412:Propanolamines / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C085075:CGP 55845A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline