Autism Spectrum Disorder (ASD), a neurodevelopmental disorder (NDD), has been increasingly associated with disruption of ion channel function. The symptoms and etiology of ASD are complex and associated with dysregulation of many brain regions. Recent research suggests that individuals with ASD have disrupted activity in the mesostriatal network, which is well-studied for its contribution to social behavior and social reward. Another developing area in the etiology of ASD are ion channel mutations. Specifically, the Kv7 ion channel family, encoded by the genes KCNQ1-5, have become increasingly implicated with NDDs such as ASD. Though broadly expressed throughout the nervous system, these channels are also expressed in the Ventral Tegmental Area (VTA), a region within the mesostriatal pathway that plays a key role in social behavior and social reward. Here we study the impact of a KCNQ3 mutation identified in multiple ASD patients, KCNQ3-R230C. To do this, we used transgenic mice and viral strategies to drive the expression of human wildtype (hKv7.3/WT) or mutant (hKv7.3/R2C) KCNQ3 in the VTA. I helped to conduct a three-chamber social interaction task wherein these transgenic mice could elect to interact with either a novel mouse or a familiar mouse, and I helped analyze the data therefrom. We observed a loss of social novelty preference in the three-chamber social interaction task in mice expressing hKv7.3/R2C but not in controls expressing hKv7.3/WT. This research contributes to our understanding of the role of ion channel disruptions in the VTA in the context of social behavior and ASD.

Prosocial behavior is important to many species and its disruption is a hallmark symptom of many diseases and disorders including autism, schizophrenia, and depression. The neurotransmitter dopamine modulates neuronal activity in the nucleus accumbens (NAc) and plays a critical role in the regulation of prosocial behavior. While the role of dopamine (DA) is well studied in the context of social behavior, little is known about neuronal activity in the NAc during social behavior. Here we use transgenic mice, viral delivery of genetically encoded fluorescent calcium sensors, and a miniaturized microscope to measure NAc neuronal activity during a series of social behavior assays. We used the 3-chamber assay to investigate NAc encoding of social novelty preference, a 5 minute on-off free social interaction assay, and an operant social task in which mice press a lever to gain access to another mouse. Preliminary data suggests that the technique is feasible to detect neuronal activity in the NAc during social behavior, and that there is no detectable encoding of social novelty preference in the 3-chamber assay. Findings from this study will improve our understanding of how prosocial behavior is encoded and may lead to the development of treatments for diseases and disorders that result in a loss of prosocial behavior.