Evaluation of seizure foci and genes in the Lgi1L385R/+ mutant rat

•EEG Lgi1L385R/+ rats showed patterns that corresponded to seizure behavior.•Neural activity is increased in the lateral temporal lobe, including auditory cortex.•Microarray analysis identified candidate genes responsible for audiogenic seizures.

Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic–clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically relevant features of Lgi1 heterozygous mutant rats (Lgi1L385R/+) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1L385R/+ and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1L385R/+ rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1L385R/+ rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1L385R/+ rats are useful as an animal model of human ADLTE.