Hippocampal deletion of Na_V1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of Dravet Syndrome.

ABSTRACT: Dravet Syndrome is a severe childhood epileptic disorder caused by haploinsufficiency of the SCN1A gene encoding brain voltage-gated sodium channel Na_V1.1. Symptoms include treatment-refractory epilepsy, cognitive impairment, autistic-like behavior, and premature death. The specific loci of Na_V1.1 function in the brain that underlie these global deficits remain unknown. Here we specifically deleted Scn1a in the hippocampus using the Cre-Lox method in weanling mice. Local gene deletion caused selective reduction of inhibitory neurotransmission measured in dentate granule cells. Mice with local Na_V1.1 reduction had thermally evoked seizures and spatial learning deficits, but they did not have abnormalities of locomotor activity or social interac

SUBMITTER: Stein RE 

PROVIDER: S-EPMC6697805 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature