Neural mechanisms underlying autism behaviors in SCN1A mutant mice

Electrical signals in neurons rely on the proper function of voltage‐gated sodium channels. Mutations in the gene SCN1A, which encodes voltage‐gated sodium channel type 1 (Nav1.1 channels), cause Dravet syndrome — a severe childhood neuropsychiatric disorder characterized by epilepsy, cognitive deficits and autism‐like behaviors.

In 2006, William Catterall and his colleagues at the University of Washington created a mouse model of this disorder. They observed that inhibitory neurons in the brains of these mice function improperly, which results in electrical signals being generated in an uncontrolled manner. These mice also show severe cognitive deficits and autism‐like behaviors, including hyperactivity, anxiety and social deficits. For Catterall’s team, the next crucial step in analyzing the mice is to identify the brain circuits most affected by the mutations.

The researchers plan to measure neuronal activity in different regions of the brain in control and mutant mice, both at rest and during social and cognitive behaviors. Correlations in electrical activity among different brain regions may reveal patterns that underlie impaired versus healthy cognition and behavior. Then, the researchers plan to treat the mutant mice with drugs that enhance the inhibitory action of neurons and record the changes in both neuronal electrical activity and behavior. The results may offer new insight into the neural circuits adversely affected by mutation of Nav1.1 channels. They may also open the way for additional studies of the mechanistic basis of cognitive and behavioral deficits seen in people with autism spectrum disorders.