Infant attachment to a caregiver is required for the typical development of social behavior and reduces the lifetime risk for mental illness. The underlying molecular and neural mechanisms of infant attachment to a caregiver are not well-characterized. Oxytocin (OXT) plays an important role in adult social behavior and has been hypothesized to play a role in infant attachment. This proposal will test a specific modulatory role for OXT acting at peripheral OXT receptors (OXTR) in infant attachment-related brain and behavior development. We have recently identified OXTR in the periphery of infant mice, including the face and oronasal cavity. Given the presence of OXT in maternal fluids such as saliva and breast milk, this suggests a simple hypothesis that maternal OXT could bind to infant peripheral OXTR to bias brain and behavioral development toward the social environment. In this proposal, we will determine the brain and behavioral effects of OXT acting upon peripheral OXTR in infant mice. First, we will perform anatomical studies to define the relevant circuitry from the periphery to the brain. Second, we will determine if these peripheral OXTR play a role in social orienting and contact behavior in neonates. Finally, we will determine if these peripheral OXTR influence the development of a key player in later social behavior- the infant?s own OXT production. Individual differences in the levels of OXT contribute to individual differences in social behavior and mental health. However, we know very little about how these individual differences in OXT are influenced by social contact in development or how social stimuli elicit OXT activity the socially nave infant brain. This proposal will help address these knowledge gaps. Using infant mice, the long-term goals of this project are to understand 1) how social contact is transduced into the infant brain, 2) how the socially nave neonate responds to exogenous OXT at the level of brain and behavior in the neonatal period, and 3) how social contact influences individual differences in OXT levels in the neonate. In addition, by performing these studies in male and female infant mice, we will ascertain potential sex differences in the acute response to social contact and OXT in the neonatal period. Further, because these experiments will clarify the roles of OXTR in the oronasal cavity, the findings may have broader applicability for understanding the mechanism of action of intranasal delivery of clinical doses of OXT. These experiments will determine the mechanisms of acute change in the neonate, with the potential for future experiments to determine the mechanisms of the long term effects of these changes.
Social contact during the infant period is necessary for healthy development, but how this works is not well- understood. This research, using male and female newborn mice, will examine how social contact influences the development of the brain and behavior. This knowledge is important to improve prevention and intervention strategies for better health outcomes in development and adulthood.
