Dravet syndrome (DS) is an intractable childhood epilepsy syndrome accompanied by mental disability, behaviors similar to autism, and premature death. DS is caused by dominant loss-of-function mutations in the gene encoding the Na V 1.1 sodium channel, SCN1A, which initiates electrical signals in the nerve cells of the brain. The physiological basis for this disease is largely unknown. Here we describe the functional effects of DS mutations on inhibitory neurons in the cerebral cortex in mice. Our results show that two major types of inhibitory neurons are impaired in generation of electrical signals by a DS mutation, whereas excitatory neurons are unaffected. The resulting imbalance of excitatory over inhibitory electrical signaling would contribute in an important way to the symptoms of DS.

Abstract