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Significance Dravet Syndrome is an intractable epileptic disorder that includes cognitive and social-interaction deficits. It is caused by loss-of-function mutations in the brain sodium channel NaV 1.1. We asked whether symptoms of Dravet Syndrome could be induced by introducing the mutation only in the hippocampus, a brain region important for learning and memory and for control of brain excitability. Local mutation of NaV 1.1 specifically reduced the excitability of inhibitory neurons in the hippocampus. This local mutation caused thermally evoked seizures and spatial learning deficits, which are brain-wide effects. Our results point to a key role for the hippocampus in generating epilepsy and cognitive deficit in Dravet Syndrome and suggest that gene therapy targeting the hippocampus might be effective in this devastating disease.

Hippocampal deletion of Na V 1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of Dravet Syndrome

Hippocampal deletion of Na _V 1.1 channels in mice causes thermal seizures and cognitive deficit characteristic of Dravet Syndrome