24.5 GENETIC REGULATION OF SOCIAL ATTACHMENT BEHAVIORS

Abstract

Devastating conditions such as autism spectrum disorder (ASD) and schizophrenia manifest with a dramatic disruption and persistent collapse of interpersonal interactions early in life, and social functioning is a key predictor of outcome. It has been difficult to study social attachment because traditional genetic lab model animals do not exhibit adult social attachment behaviors. Thus, the analysis of social attachment has been resistant to genetic and neurobiological approaches. Prairie voles, in contrast, display social attachment as adults such that mating partners form an enduring pair bond and display complex attachment behaviors, such as social monogamy and biparental care. Pioneering work in the prairie vole has identified vasopressin (Avp) and oxytocin (Oxt) as critical mediators of pair bonding in voles and social cognition and behaviors in humans. These findings indicate that the genetics and neural control of social attachment may be conserved between humans and prairie voles. We are, for the first time, well-poised to understand how specific genes and pathways function in the circuits underlying social attachment and contribute to distinct aspects of attachment and cognitive processes. We established molecular genetic approaches in prairie voles using CRISPR-mediated mutagenesis. We generated animals mutant for OxtR, as well as genes strongly associated with ASD and schizophrenia, in particular SHANK3, Scn2a, and Drd2. In parallel, we have begun studies to characterize changes in gene expression and neural activity in regions of the vole brain that control attachment-related behaviors. Here, we present our analysis of the behavioral, molecular, and physiologic consequences of loss of OxtR, as well as phenotypes associated mutations in genes associated with neuropsychiatric disorders. We demonstrate that social attachment in voles is controlled by genetically separable pathways, with individual genes controlling sex-specific aspects of pair bonding and attachment behaviors, analogous to endophenotypes observed in clinical populations.