Our lab uses voles to better understand the genetic, molecular, systems, and environmental regulation of social behavior. Unlike other rodent models, monogamous prairie voles are highly social and form strong social bonds with their mates, making them an ideal candidate to investigate, among other things, the biological basis of social bonds. Psychiatric disorders such as autism spectrum disorder, schizophrenia, and depression are associated with severe impairments in the social domain. Understanding the neurobiological and genetic mechanisms underlying the regulation of normal social behavior will provide insights into the systems that may be disrupted in these devastating disorders.
Genetic variation underlying diversity in social behavior
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 both candidate gene and genomic approaches.
Previous work in voles and other rodents has established that vasopressin acting on vasopressin V1a receptor mediates a wide variety of species-typical social behaviors. Selective breeding experiments and in vitro gene expression assays indicate that length variation in a microsatellite located in the 5' flanking region of the V1a receptor gene may modulate receptor expression and vasopressin-dependent social behaviors. We are working to better understand the definitive role of this region's influence on gene expression and elucidate the mechanism underlying these microsatellite-mediated differences.
While candidate gene approaches have identified a handful of key genes that influence social behaviors, complex sociobehavioral phenotypes result from the actions of many genes. In order to identify additional candidate genetic loci that influence social behavior, we are generating linkage maps and conducting selective breeding studies to isolate specific genetic loci involved in social behaviors.
Genetic manipulation of social behavior
Genetic manipulation techniques have been instrumental in our investigation of social behavior. Our lab uses two general approaches to alter gene expression in both voles and mice. While germline genomic manipulation is not yet possible in voles, use of viral vectors to alter gene expression in specific brain regions provides insight into some of the key molecular players that influence social bonding. For instance, virally mediated transfer of vasopressin receptor 1a into a part of the central reward circuitry of non-monogamous meadow voles alters their behavior to be more monogamous-like. This work established that the specific brain distribution of this receptor is integral to its species specific actions on behavior.
Additionally, when possible, we use mouse models to test genetic hypotheses developed from our work with voles. By doing so, we are able to marry the novel sociobehavioral traits observed in voles with the power of mouse genetics. In addition to working with traditional mouse knockouts, we have also generated transgenic mice expressing the prairie vole vasopressin V1a receptor under the control of its endogenous promoter. These mice display a V1a receptor patterns similar to that of prairie voles and increases in affiliative behavior when administered vasopressin. We are continuing to explore the frontiers of genetic manipulation in mice and voles.
Pharmacological treatments for the sociobehavioral deficits of autism
Social bonding in the prairie vole has the potential to be used as an animal model for the development of novel pharmacotherapies for the treatment Autism Specturm Disorder (ASD). Genetic and pharmacological studies have implicated oxytocin dysregulation in the impairments associated with autism. Variation in oxytocin receptor system has also been found by our lab to strongly influence social behavior both within prairie voles and between prairie and the asocial meadow voles. Currently we are testing the drugs targeting both the oxytocin and the glutamate receptors systems for their ability to enhance social bonding in the voles. Many of these drugs are simultaneously being tested in humans with autism for their effects on the social impairments that define the disorder. Through verification that drugs which enhance social bonding in the prairie voles also enhance social behavior in humans with social deficits, we hope to establish strong predictive validity for the prairie vole model, which will allow us to use this model to develop drugs for the treatment of autism.
Effects of social environment on molecular systems and behavior
Social environment shapes both biological characteristics and behavior. Because prairie voles form strong social bonds between mates and have biparental family units, they provide a novel model for studying the effects of social loss. Ongoing studies in our lab have been investigating the effects of separating mates within this monogamous species as a potential model for social-loss induced grief and depression. Other studies are looking at the long term effects of family unit composition and maternal deprivation on formation of stress systems and behavior.