Neural Circuitry of Social Behavior
Through several lines of experimental inquiry, our lab has begun to establish a clear neuromodulatory role for oxytocin signaling in the facilitation of social information processing. Mating is an essential component of normal pair bond formation in the prairie vole, and central release of oxytocin during mating is well established. What remains unknown, however, is how oxytocin mediates critical changes in brain circuitry to ultimately give rise to a lasting pair bond.
We are working to address this fundamental knowledge gap using multiple experimental techniques. Pharmacological studies in our lab show distinct differences in patterns of brain activation following mating when the oxytocin system is blocked through administration of an oxytocin antagonist prior to testing. Electrophysiological correlates of social information processing further demonstrate enhanced network coherence facilitated by oxytocin.
Finally, optogenetic stimulation of central oxytocinergic fiber projections to artificially induce a partner preference will demonstrate the sufficiency of central oxytocin in the formation of social bonds.Beyond the induction of social bonds following mating, a variety of bond maintenance behaviors can be observed in the prairie vole, many with translational implications for human social behavior. The ability to sense and respond to the emotions of others is vital to normal social interactions and the maintenance of relationships.
To understand the neurobiological mechanisms underlying empathic behavior, animal models must be developed. We have recently discovered that prairie voles will demonstrate consoling behavior towards their mates when the mate is distressed. Using behavioral, pharmacological and genetic manipulations, we have thus far demonstrated an important role of oxytocin neuromodulation in this empathy-based consoling response.
Neurogenetics of Social Cognition
Behavioral diversity is driven by a combination of genetic and environmental influences. In order to better understand the contribution of genetic variation in shaping behavioral differences, our lab is employing candidate gene and genomic approaches.
Previous work in voles and other rodents has established that vasopressin acting on the vasopressin V1a receptor, and oxytocin acting on the oxytocin receptor, mediate a wide variety of species-typical social behavior. We have shown that expression of these receptors is quite variable in the brain, both between species and within individuals from the same species. We are currently investigating how genetic polymorphisms influence transcriptional mechanisms mediating oxytocin receptor expression in the nucleus accumbens and subsequent social behaviors. In addition to baseline behavioral differences resulting from these transcriptional events, receptor density may confer resiliency or susceptibility to the developmental impact of environmental stressors such as infection. Broadly, this research is motivated by the question of how changes in gene regulation can contribute to the evolution of social behavior and brain organization, including ways in which those systems become dysfunctional in disorders of social cognition.
Using receptor autoradiography and in situ hybridization, another focus in our lab has been to determine the distribution of OT and AVP receptors in the rhesus macaque and the monogamous coppery titi monkey. In primates, OXTR is much more restricted than AVPR1A. And in contrast to rodents, which express OXTR heavily in olfactory processing regions, primates express OXTR in regions involved in visual information processing, gaze and visual attention. Current research includes investigating the distribution of OXTR in the human brain. While our work in mice and voles shows that oxytocin and vasopressin receptors (OXTR and AVPR1A) play important roles in social recognition and social bonding, recent data has suggested that variation in the oxytocin receptor gene predicts face recognition in humans. Therefore, we are expanding our scope of genetic research to explore the contribution of variation in OXTR and AVPR1A genes to variation in chimpanzee social behavior. The results of this research suggest that a polymorphic region in chimpanzee AVPR1a promoter predicts social personality traits and joint attention. As rodents use smell, and humans use visual cues for social recognition, our findings suggest that there is a remarkable evolutionary conservation in the role of oxytocin in social cognition from rodent to man that transcends the sensory modalities used.
Translational Social Neuroscience
Partner preference formation in prairie voles is a complex social cognitive process that involves social information processing (mediated by oxytocin), social reward and reinforcement (mediated by dopamine and opiates), and social learning. As partner preference formation requires oxytocin neurotransmission, this behavioral paradigm is useful for assessing oxytocin-mediated cognitive processes and thus has face, construct and predictive validity for screening therapeutic approaches to enhance human social cognition. Within the prairie vole model, we are currently investigating pharmacological approaches to stimulate oxytocin release and, subsequently, enhance social cognition to facilitate partner preference formation. Genetic and pharmacological studies have implicated oxytocin dysregulation in some of the social impairments associated with autism spectrum disorder. Thus, compounds with the ability to enhance or promote oxytocinergic signaling could represent potential novel treatments for psychiatric disorders known to affect social functioning.
In non-human primates, these same novel pro-social compounds are being investigated for their potential effects not only in standard laboratory behavioral testing but also in free run/group settings. Rhesus macaques living in large social groups exhibit a variety of behaviors unable to be observed in rodent species, making them ideal for the study of social networks. Indeed, these social groups are an important component of our studies designed to investigate how manipulation of socially-implicated neural circuitry (e.g. administration of prosocial compounds) affects not only the behavior of the experimental individual within the social network, but how other members of the network respond to them.
Translational neuroscience studies have revealed that the neuropeptide oxytocin promotes social functioning by acting on fundamental processes such as attention to relevant social cues and reward sensitivity to these cues. Current studies in our laboratory are underway to examine the effects of intranasal oxytocin on social behavior using functional imaging techniques with the idea that by acting on key perceptual and emotional brain regions, oxytocin can improve social functioning for people suffering from autism and other social disorders.
By conducting experiments in a variety of species with differing levels of social complexity, our goal is to create seamless transitions from the laboratory to the clinic. We believe manipulation of the oxytocin system holds great promise as a potential therapeutic treatment for psychiatric disorders characterized by deficits in social functioning. To this end, we are conducting further studies on the effect of intranasal oxytocin administration in humans with autism spectrum disorder. Through a combination of novel behavior and neuroimaging techniques, we aim to better understand how intranasal oxytocin modifies neural activity to facilitate prosocial behavior.