Somatostatin-Positive Interneurons Contribute to Seizures in SCN8A Epileptic Encephalopathy.

ABSTRACT: SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant SCN8A, which encodes the voltage-gated sodium channel Na_V1.6. To date, it is unclear if and how inhibitory interneurons, which express Na_V1.6, influence disease pathology. Using both sexes of a transgenic mouse model of SCN8A epileptic encephalopathy, we found that selective expression of the R1872W SCN8A mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. Patch-clamp electrophysiology experiments revealed that SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediate

SUBMITTER: Wengert ER 

PROVIDER: S-EPMC8570835 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature