Dysregulation of GABAergic System in the Hippocampus and Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy

Abstract

AbstractEpilepsy is tightly associated with dysfunction of inhibitory γ-aminobutyric acid (GABA) neurotransmission. In this study, Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5-2 months and fully developed AGS expression by 3rdmonth. We analyzed GABAergic system of the inferior colliculi (IC) and the hippocampus of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl−cotransporter 1 (NKCC1) expression was increased, while in adults K+/Cl−cotransporter 2 (KCC2) was downregulated indicating impairment of postsynaptic GABA action both at early and later stages of postnatal development. In the hippocampus of young KM rats, we observed a decrease in activity of GABAergic neurons and downregulation of KCC2 and NKCC1. Adult rats, in opposite, demonstrated elevated activity of the hippocampal GABAergic cells and unchanged expression of chlorine transporters indicating upregulation of GABA transmission. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats, while in the hippocampus, upregulation of GABAergic system can restrict the spreading of epileptiform activity from the brainstem.