Neurological and psychiatric syndromes often have multiple disease traits, yet 
it is unknown how such multi-faceted deficits arise from single mutations. 
Haploinsufficiency of the voltage-gated sodium channel Nav1.1 causes Dravet 
syndrome, an intractable childhood-onset epilepsy with hyperactivity, cognitive 
deficit, autistic-like behaviours, and premature death. Deletion of Nav1.1 
channels selectively impairs excitability of GABAergic interneurons. We studied 
mice having selective deletion of Nav1.1 in parvalbumin- or 
somatostatin-expressing interneurons. In brain slices, these deletions cause 
increased threshold for action potential generation, impaired action potential 
firing in trains, and reduced amplification of postsynaptic potentials in those 
interneurons. Selective deletion of Nav1.1 in parvalbumin- or 
somatostatin-expressing interneurons increases susceptibility to 
thermally-induced seizures, which are strikingly prolonged when Nav1.1 is 
deleted in both interneuron types. Mice with global haploinsufficiency of Nav1.1 
display autistic-like behaviours, hyperactivity and cognitive impairment. 
Haploinsufficiency of Nav1.1 in parvalbumin-expressing interneurons causes 
autistic-like behaviours, but not hyperactivity, whereas haploinsufficiency in 
somatostatin-expressing interneurons causes hyperactivity without autistic-like 
behaviours. Heterozygous deletion in both interneuron types is required to 
impair long-term spatial memory in context-dependent fear conditioning, without 
affecting short-term spatial learning or memory. Thus, the multi-faceted 
phenotypes of Dravet syndrome can be genetically dissected, revealing synergy in 
causing epilepsy, premature death and deficits in long-term spatial memory, but 
interneuron-specific effects on hyperactivity and autistic-like behaviours. 
These results show that multiple disease traits can arise from similar 
functional deficits in specific interneuron types.