The function of SCN2A in neocortex

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Title: The function of SCN2A in autism spectrum disorder Project Summary: Mutations identified by exome sequencing demonstrate that disruption of the sodium channel SCN2A is strongly associated with autism spectrum disorder. SCN2A encodes the neuronal sodium channel NaV1.2, which is expressed at the site of action potential initiation. More recently, we have discovered that these channels are likely expressed throughout neocortical excitatory neuron dendrites, and that their dendritic function may be consequential to synaptic maturation and plasticity. Here, we will use a complement of electrophysiology, 2-photon imaging, and compartmental modeling to determine how heterozygous and homozygous loss of function of Scn2a affects the integrative properties of neurons. Furthermore, we will use novel mouse models and genetic techniques to ask whether changes in Scn2a expression levels in particular cell classes and developmental stages alters neuronal function. Results of this study will provide critical insight into how mutations in SCN2A contributes to autism spectrum disorder and the activity dependent development of cortical circuits.