Imbalance of glutamatergic and GABAergic neurotransmission in audiogenic seizure-susceptible L ()-mutant rats.

() was identified as a causative gene of autosomal dominant lateral temporal lobe epilepsy. We previously reported that -mutant rats carrying a missense mutation (L385R) showed audiogenic seizure-susceptibility. To explore the pathophysiological mechanisms underlying Lgi1-related epilepsy, we evaluated changes in glutamate and GABA release in -mutant rats. Acoustic priming (AP) for audiogenic seizure-susceptibility was performed by applying intense sound stimulation (130 dB, 10 kHz, 5 min) on postnatal day 16. Extracellular glutamate and GABA levels in the hippocampus CA1 region were evaluated at 8 weeks of age, using microdialysis techniques. Under naïve conditions without AP, glutamate and GABA release evoked by high-K depolarization was more prominent in -mutant than in wild-type (WT) rats. The AP treatment on day 16 significantly increased basal glutamate levels and depolarization-induced glutamate release both in -mutant and WT rats, yielding greater depolarization-induced glutamate release in -mutant rats. On the other hand, the AP treatment enhanced depolarization-induced GABA release only in WT rats, and not in -mutant rats, illustrating reduced GABAergic neurotransmission in primed -mutant rats. The present results suggest that enhanced glutamatergic and reduced GABAergic neurotransmission are involved in the audiogenic seizure-susceptibility associated with -mutation.