Authors:

Christian A Durbin

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The Scn2a gene encodes for voltage-gated sodium channel NaV1.2, which is responsible for initiation and propagation of action potentials. Mutations in Scn2a are among the leading monogenic causes of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Scn2a deficiency has been proposed to be linked with ASD, which may offer another target for treating ASD symptoms. Our lab developed an Scn2a-deficient mouse model that exhibits reduced levels of NaV1.2 and social deficits, recapitulating the molecular and behavioral phenotypes in human children with ASD. To analyze deficits in neural activity associated with social deficits in our mouse model, we use in vivo calcium imaging to measure activity in the nucleus accumbens (NAc), which receives projections from the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), known regions encoding social behavior. Since the NAc is an important brain region for social behavior via VTA and mPFC circuits, we hypothesize that deficits in neuronal activity due to Scn2a deficiency like hyperexcitability will impair neuronal activity linked to social behavior in the NAc of mice, suggesting an impairment of the signal-to-noise ratio in the NAc linked to social behavior. Our results indicate that our Scn2a-deficient mice exhibit a lower signal-to-noise ratio than wild-type mice during social behavior, suggesting that deficits in NAc function are associated with social deficits in Scn2a-deficient ASD models. In future experiments, genetic rescue of Scn2a-deficient mice models may identify the NAc as a potential target for treating social deficits in ASD. Keywords: Autism Spectrum Disorder; Nucleus Accumbens; Social Behavior; SCN2A

Source:

Purdue University / 2024

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Co-authors:

Christian A Durbin