Neuromodulatory mechanisms mediating social attachment behaviors

About This Grant

PROJECT SUMMARY Social attachments play a central role in most, if not all, levels of human interaction, from parent-child attachment to enduring partnerships with mates. Many neuropsychiatric disorders manifest with severe disruptions to interpersonal interactions, significantly impacting health and relationships. Despite the importance of attachment, little is known about the neural pathways mediating these behaviors, or how they are impacted by environmental or genetic factors that disrupt relationships. Prairie voles (Microtus ochrogaster) form social attachments to their mates (pair bond) and demonstrate enduring social monogamy. Pair bonded prairie voles prefer huddling with their partners and aggressively reject other potential mates, providing a powerful system to understand the fundamental mechanisms that mediate the formation and expression of enduring attachments. Pioneering work identified the peptide hormones vasopressin (Avp) and oxytocin (Oxt) as critical mediators of pair bonding and complex social behaviors in diverse species, including humans. The deep similarity in genetic and neuroanatomic structures between humans and other eutherian mammals and the conserved roles of these hormones throughout vertebrates suggests that findings in the prairie vole model may inform our understanding of human attachment behaviors. To understand behavioral modules underlying social attachment and their genetic, molecular, and neural architecture, we developed 1) a rigorous battery of social behavior paradigms, 2) tools for genomic analysis, and 3) in vivo imaging approaches to monitor neural activity, coupled with 4) molecular genetics in prairie voles, to analyze distinct components of attachment behaviors. Our recent work has revealed previously unappreciated nuances in the neuromodulatory control of pair bonding. We find that signaling by the oxytocin (Oxtr) and vasopressin 1a receptors is strikingly not required for the formation of partner. Rather, Oxtr function controls the timing and promiscuity of pair bonding and influences reciprocal social interactions between mates. Using unbiased profiling of gene expression, characterization of expression changes in components of various neuromodulatory pathways, in vivo imaging of the activity of other neuromodulatory systems, and pharmacologic manipulations of these pathways in specific brain regions, we find that separate signaling pathways appear to regulate distinct components of social attachment behaviors. Here, we extend these studies to determine how these and other neuromodulatory pathways act, and interact, in specific brain regions across the formation of bonds and subsequent social interactions to influence enduring social relationships between mates.