Diminished presynaptic GABA(B) receptor function in the neocortex of a genetic model of absence epilepsy.
Changes in GABA(B) receptor subunit expression have been recently reported in the neocortex of epileptic WAG/Rij rats that are genetically prone to experience absence seizures. These alterations may lead to hyperexcitability by downregulating the function of presynaptic GABA(B) receptors in neocortical networks as suggested by a reduction in paired-pulse depression. Here, we tested further this hypothesis by analyzing the effects induced by the GABA(B) receptor agonist baclofen (0.1-10 microM) on the inhibitory events recorded in vitro from neocortical slices obtained from epileptic (>180 day-old) WAG/Rij and age-matched, non-epileptic control (NEC) rats. We found that higher doses of baclofen were required to depress pharmacologically isolated, stimulus-induced IPSPs generated by WAG/Rij neurons as compared to NEC. We also obtained similar evidence by comparing the effects of baclofen on the rate of occurrence of synchronous GABAergic events recorded by WAG/Rij and NEC neocortical slices treated with 4-aminopyridine + glutamatergic receptor antagonists. In conclusion, these data highlight a decreased function of presynaptic GABA(B) receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures.
Inaba
Yugi
Y
Montreal Neurological Institute and Departments of Neurology and Neurosurgery, and Physiology, McGill University, Montréal, Que., Canada.
D'Antuono
Margherita
M
Bertazzoni
Giuliano
G
Biagini
Giuseppe
G
Avoli
Massimo
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D002462:Cell Membrane / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004832:Epilepsy, Absence / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000008:administration & dosage; D058786:GABA-B Receptor Agonists; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008839:Microelectrodes; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D018080:Receptors, GABA-B / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D026902:Potassium Channel Blockers; D018080:Receptors, GABA-B; D015761:4-Aminopyridine; D001418:Baclofen