The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex.

ABSTRACT: Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein Na_V1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here we show that Na_V1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons in addition to regulating early developmental axonal excitability. Na_V1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic stren

SUBMITTER: Spratt PWE 

PROVIDER: S-EPMC7935470 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature