The properties of reticular thalamic neuron GABA(A) IPSCs of absence epilepsy rats lead to enhanced network excitability

Abstract

Both human investigations and studies in animal models have suggested that abnormalities in GABA(A) receptor function have a potential role in the pathophysiology of absence seizures. Recently we showed that, prior to seizure onset, GABA(A) IPSCs in thalamic reticular (NRT) neurons of genetic absence epilepsy rats from Strasbourg (GAERS) had a 25% larger amplitude, a 40% faster decay and a 45% smaller paired-pulse depression than those of nonepileptic control (NEC) rats. By means of a novel mathematical description, the properties of both GAERS and NEC GABAergic synapses can be mimicked. These model synapses were then used in an NRT network model in order to investigate their potential impact on the neuronal firing patterns. Compared to NEC, GAERS NRT neurons show an overall increase in excitability and a higher frequency and regularity of firing in response to periodic input signals. Moreover, in response to randomly distributed stimuli, the GAERS but not the NEC model produces resonance between 7 and 9 Hz, the frequency range of spike-wave discharges in GAERS. The implications of these results for the epileptogenesis of absence seizures are discussed.