Buschman, Timothy JLenzi, Michael2022-07-152026-09-292022-07-152026-09-292022-04-222022-07-15http://arks.princeton.edu/ark:/88435/dsp01cn69m731hhttps://theses-dissertations.princeton.edu/handle/88435/dsp01cn69m731hAutism Spectrum Disorder (ASD) is a pervasive disorder mostly diagnosed in young children. Some studies have estimated the rates of ASD in the U.S. to be around 2-3 percent of children, so it is a somewhat common disorder that has gained a large interest from the scientific community. There are many etiologies that are known and studied, and many are genetic such as the SHANK family of genes. While these genes have been extensively studied in the literature, the effect of zygosity is not well studied. One aim of this thesis is to look at a heterozygous and a homozygous knockout model of SHANK3b and compare differences between these etiologies in behavior and cortical brain dynamics to better understand the effect of zygosity. This will be done through a series of behavioral assays that will assess the presence of repetitive behaviors and social deficits: two behaviors that are characteristic of autism. This study also aims to use widefield calcium imaging to investigate how molecular changes lead to a brain-wide scale of atypical functional connectivity. Our results show higher repetitive behaviors in grooming but not in digging for both models of ASD. Our data regarding zygosity in our grooming tests suggest a linear relationship between repetitive behavior and severity of zygosity. Our social tests show an overall trend of less social activity in the heterozygous knockout mice compared to controls, and more social activity in the homozygous knockout mice compared to controls. This suggests an interesting relationship between zygosity and social behaviors that would need to be further explored in a future study.application/pdfenPrinceton University Senior Theses