Project Title: Exploring Endophenotypes of Mouse Social Behavior Principal Investigator: Garet Lahvis, PhD Many neurodevelopmental disorders, including autism, fragile X syndrome, and schizophrenia, feature aberrant social behavior as a core characteristic. These disorders feature a broad array of social impairments, ranging from deficits in shared attention, to communication delays, to social withdrawal. The underlying genetic causes of these social impairments remain largely unknown. Mouse models have tremendous value for elucidating the roles of genes in development. To more fully understand the genetics of social behavior, we propose an expanded panel of mouse behavioral tests that allow us to explore the smallest function units of social behavior, or social endophenotypes. Specifically, three features of social functioning will be evaluated: the extent to which a social stimulus affects a trained goal-directed behavior, the extent to which social interaction can serve as reward/reinforcement, and the degree that a social stimulus can serve as a spatial cue for learning and memory. We propose to determine if these endophenotypes can be distinguished in five common inbred mouse strains. We then propose to determine if these endophenotypes are anomalous in knockout mice with known deficits in social behavior. We will evaluate knockout strains that have known deficits in social recognition, nurturing behavior, and social congregation. It is expected that some of the knockout mice will exhibit more profound deficits in these measures than both wild-type littermates and the five background strains. By developing new measures of mouse social endophenotypes, we can more precisely delineate the roles of particular genes in social functionality. In future projects, this work is likely to provide greater understanding of the neurobiological mechanisms underlying the social impairments that are associated with developmental disorders, such as autism.

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