Characterization of the Transcriptome in an Emerging Model for Social Behavior

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (01): Behavior, Behavioral Change, and Prevention and specific Challenge Topic, 01-GM-102: Model organisms for social behavior studies. Identification and development of model organisms that allow for integrative analyses of the genetic, biochemical, physiological, and environmental components of social behavior. Mental health disorders, including autism spectrum disorders, schizophrenia and depression, are characterized in part by severe impairments in social behaviors including social reciprocity, social cognition and social motivation. Unfortunately, because of the limited social repertoire of traditional animal models such as mice and rats, our understanding of the genetic and neurobiological mechanisms that govern social behaviors are poorly understood. Consequently, pharmacological interventions to treat deficits in social behaviors have met with little success. However, the prairie vole (Microtus ochrogaster) is rapidly emerging as a premier model organism for understanding the fundamental neurobiology of social behaviors. In contrast to more established rodent models such as mice and rats, voles demonstrate a much richer and diverse range of complex social behaviors. For instance, socially monogamous prairie voles are highly affiliative, form life-long pair bonds with their mates, and both parents provide extensive care of their young. In contrast, meadow voles (M. pennsylvanicus) are relatively asocial, do not form social attachments of any sort, and are uniparental. Comparative studies between vole species have already led to the identification of several genes and neural pathways that contribute to variation in social behaviors, yet, largely because of a lack of genomic resources for these species, research has been limited to the study of a handful of candidate genes. The goal of this research proposal is to advance the development of the prairie vole as an extraordinary model organism for understanding the biological underpinnings of social behaviors by developing a key genomic resource, a catalog of vole gene sequences. Specifically we will 1) generate partial or complete gene sequences for 18,000 vole genes that encompass > 50% of the transcriptome, and 2) for the first time examine the nature of social bond formation on a genome-wide scale. In summary, this research project will generate a critical resource for an emerging model of human social behavior and will likely lead the discovery of novel gene pathways involved in the regulation of complex social behavior such as social bonding. These discoveries may ultimately lead to novel pharmacological interventions to enhance social cognitive function in autism, schizophrenia, or depression. PUBLIC HEALTH RELEVANCE: Animal models are critical for discovering the genetic, biochemical, physiological and environmental components of social behavior. The goal of this research project is to develop a key resource needed to exploit an emerging animal model system that has proven utility for understanding the biological and environmental mechanisms of social behavior in humans related to alcoholism, autism, parental care, and pair-bonding.