Social recognition (the ability to discriminate between familiar and unfamiliar individuals) is essential for appro- priate and beneficial social interactions. Conversely, social recognition deficits are observed in autism spec- trum disorders (ASD). ASD is diagnosed early in life and shows a strong male-bias in incidence and symptom severity. This drives the need to understand the neural basis of social recognition and to study this in both sex- es and at an early age. The vasopressin (VP) and oxytocin (OT) systems are ideal candidates to study the neural basis of social recognition because they modulate social recognition in humans and animals, show sex and age differences in the brain, have been implicated in ASD, and emerge as potential drug targets in the treatment of social dysfunction. The long-term goal of this research is to reveal the neuronal mechanisms and pathways by which VP and OT regulate social recognition in both sexes and at both juvenile and adult ages. We will use rats as model organism because social recognition is well defined in rats and the VP and OT sys- tems are highly conserved across mammalian species. The overall hypothesis is that VP and OT systems function differently in both sexes and at both ages to regulate social recognition. In support, we showed that administration of VP into the lateral septum (LS) improves social recognition in juvenile females, but not in ju- venile males. Moreover, blockade of the VP V1a receptor (V1aR;main VP receptor in the brain) impaired so- cial recognition in adult males and females while it induced a preference to investigate a familiar rat over a novel rat in juvenile males and females. The objective is to determine how VP and OT in the LS regulate social recognition in sex- and age-specific ways. There are three independent specific aims that collectively will pro- vide insights into the mechanisms and pathways by which VP and OT regulate social recognition.
Aim 1 will test the hypothesis that differential LS-VP release underlies sex and age differences in the regulation of social recognition.
Aim 2 will test the hypothesis that OT regulates social recognition in sex- and age-specific ways.
Aim 3 will test the hypothesis that VP and OT in the LS regulate social recognition via sex- and age-specific modulation of LS projection areas. We will use a comprehensive approach that includes in vivo microdialysis, microinjections, anatomical pathway tracing, mapping of neuronal responses, and behavioral analysis. This approach is innovative because this will be the first comprehensive study comparing neuropeptidergic control of social recognition between the sexes and at two life stages. The proposed research is significant because VP and OT regulate social recognition in humans and outcomes may therefore have translational potential for understanding sex and age differences in the roles of VP and OT in normal and abnormal social recognition in humans.
The proposed research is relevant to public health because knowledge about sex- and age- specific regulation of social recognition by vasopressin and oxytocin will advance our understanding of sex and age differences in the regulation of behavior and will be informative for the social recognition deficits and the sex-biases in incidence, symptom severity, and treatment responses in neurodevelopmental disorders, such as autism spectrum disorders. This knowledge may also be informative for age- and sex-specific therapeutic uses of neuropeptidergic agents in the treatment of social dysfunction. The proposed research is relevant to the mission of NIMH to transform the understanding and treatment of mental illnesses.
