Characterization of Hippocampal Social Memory Circuitry in a Mouse Model of Autism Spectrum Disorder Associated Behaviors

Abstract

Autism Spectrum Disorders (ASD) are a prevalent group of neurodevelopmental disorders that can be very disruptive to the lives of individuals. Central to ASD are symptoms associated with social dysfunction, including impaired social memory. The Shank3B KO mouse is a relevant model for ASD research, as it was engineered based on genetic data gathered from humans with ASD. Importantly, Shank3B KOs also exhibit behavioral characteristics that resemble the core symptoms of the disorder, including social memory deficits. In attempts to improve understanding of the neural mechanisms contributing to the social memory deficits presented by people with ASD, this study used immunohistochemistry to characterize the cellular and molecular properties associated with hippocampal plasticity in the social memory circuitry of Shank3B KOs. Given the developmental nature of ASD, this study focused on exploring this pathway in pups. Specifically, analysis was performed to identify mossy fiber projections from the dentate gyrus (DG) to the CA2, perineuronal nets (PNNs) in the CA2, as well as PNNs and parvalbumin positive (PV+) cells in the vCA1. Results demonstrate that Shank3B KO pups have increased CA2 volume, altered PNN expression in both the CA2 and vCA1, as well as atypical PV+ cell expression in the latter. This suggests altered maturation rates and differential plasticity properties in Shank3B KOs during development and identifies potential targets for exploration in ASD research. Overall, this study lays a foundation for future studies investigating the development of social memory dysfunction and its associated pathways in ASD-associated mouse models.