Oxytocin Ligand/Receptor Variants and Social Behavior

Project Summary/AbstractThe brain neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important roles in altering neuralcircuits that regulate social behavior. These ligands regulate normative social function in a host of areas,including social attachment, parental behavior, aggression, and complex social cognition. In pathologicalbrain/behavior conditions, many disorders are characterized by dramatic deficits in the social realm.Knowledge of the way OT and AVP alter cellular function in neurons has the potential to both identifymechanisms that produce social dysfunction and to design compounds that normalize cellular function andbehavior. The present project takes advantage of the discovery of novel OT ligand structure, and variation incellular receptors for OT and AVP in the marmoset, a species that exhibits social monogamy, infant care bymales, and a family-like social structure. The first aim will characterize the effects of ligand diversity on thealteration of behavior in a variety of social domains by using in vivo behavioral pharmacology. These domainsinclude male-female attachment, infant care, mate-defense aggression, and social cooperation/altruism. Thesecond aim will quantify the receptor pharmacology and binding characteristics of the ligand variants with thecell membrane G protein-coupled receptors for these related ligands. The final aim will define the specificmodifications in G protein-mediated cell signaling processes brought about by these ligands to determine ifligand variation that modifies social behavior does so through specific or `biased' activation of differentsignaling pathways. Collectively, these three aims will provide important insights into the ways in whichneurons and behavior are modified by OT and AVP ligand variants, leading to enhanced knowledge of theneurobiology of social behavior. The project can point to potential options for designing neuropeptide ligand-receptor complexes that could serve as effective tools to treat social dysfunction.