Social Buffering of Fear in Two Mouse Models of Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive patterns of behaviors, symptoms which manifest differently among individuals. This is due to ASD being caused by a complex interaction between genetic and environmental factors. Although ASD is not caused by a single factor, various risk genes have been identified that are associated with particular phenotypes. Among these genes are the Phosphatase and tensin homolog (PTEN) and the Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), both are involved in cellular processes that affect cell division, brain growth, and neurodevelopment. Macrocephaly and microcephaly are symptoms displayed in approximately 20% and 15% of individuals with autism, respectively, and in these same population subsets, mutations in PTEN and DYRK1A occur at a greater frequency. Two mouse models of ASD associated with PTEN and DYRK1A mutations display deficits in social and sensorimotor behaviors; however, social buffering has not yet been studied in these models. Social buffering is a phenomenon in which the presence of a conspecific diminishes the negative effects of stressors. Considering how individuals with ASD struggle with social impairments, and how social isolation increases the risk of health issues, this behavior is of interest to investigate. The objective of this project is to identify if Pten haploinsufficient and Dyrk1a cHet mice experience social buffering by measuring freezing time compared to controls. Based on social interaction deficits displayed by both models, we hypothesize that these animals will be refractory to the effects of social buffering. Testing this hypothesis is the goal of the project, which we anticipate will lead to a deeper understanding of social behavior in two models of autism, macrocephaly caused by PTEN mutations, and microcephaly caused by DYRK1A mutations.