Pathogenic MTOR somatic variant causing focal cortical dysplasia drives hyperexcitability via overactivation of neuronal GluN2C N-methyl-D-aspartate receptors.

Somatic MTOR pathogenic variant recurrently found in FCD type II resulted in overactivation of GluN2C-mediated neuronal NMDARs in neocortices of rat pups. The related and time-restricted local hyperexcitability was sensitive to subunit GluN2C-specific blockade. Our study suggests that GluN2C-related pathomechanisms might be shared in common by mTOR-related brain disorders.