Benign Childhood Epilepsy Syndromes and LGI2

The RS MacDonald funded seed-project “Benign childhood epilepsy and LGI2” aimed to establish the role of LGI2 in juvenile remitting epilepsy and in normal nervous system development and function. We have generated a mouse model in which the Lgi2 gene is deleted and that allowed us to pursue two specific aims.
These specific aims are: 1) To establish whether loss of LGI2 function results in eleptiform activity in the brains of awake and normally behaving Lgi2 mutant mice, and 2) To understand how LGI2 contributes to nervous system activity. Specific aim1 was pursued in collaboration with Dr Iris Oren who has set up (with a financial contribution of the RS McDonald trust ‘establishing a facility for recording EEG and seizures in rodents’) a facility to record EEG activity in normal behaving mice. EEGs recordings from adult Lgi2 mutant animals did not provide evidence for eleptiform activity in these mice, most likely because these animals were more than 8 weeks of age. However, electrophysiological examination of cerebellar slice cultures derived from Lgi2 mutant animals suggest that LGI2 contributes to neuronal excitability in young adolescent animals but not in adults, thus providing a possible explanation for the remitting nature of so many childhood epilepsies. We demonstrated that underlying the maturation of the neuronal system is the LGI2-mediated accumulation of voltage-gated potassium channels in axons and nerve terminals.