Changes in GABAB 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 GABAB 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 GABAB receptor agonist baclofen (0.1-10 μM) 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 GABAB receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures. Copyright © 2009 S. Karger AG, Basel.
Diminished presynaptic GABAB receptor function in the neocortex of a genetic model of absence epilepsy / Y., Inaba; M., D'Antuono; Bertazzoni, Giuliano; G., Biagini; Avoli, Massimo. - In: NEUROSIGNALS. - ISSN 1424-862X. - STAMPA. - 17:2(2009), pp. 121-131. [10.1159/000197864]
Diminished presynaptic GABAB receptor function in the neocortex of a genetic model of absence epilepsy
BERTAZZONI, Giuliano;AVOLI, Massimo
2009
Abstract
Changes in GABAB 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 GABAB 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 GABAB receptor agonist baclofen (0.1-10 μM) 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 GABAB receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures. Copyright © 2009 S. Karger AG, Basel.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.