Relationships between neuronal V1aR expression and single-nucleotide polymorphisms in Microtus ochrogaster

Studying neurobiological models of social cognition has emerged as an important way to understand the complex processes that account for social behaviors. The neuropeptides vasopressin and oxytocin are known to act on their central nervous system receptors to shape social cognition and behavior. In the prairie vole, a monogamous rodent often used for studying social cognition because of its ability to form pair-bonds, diversity in expression of vasopressin 1a receptors (V1aR) has been linked with non-coding variation at the avpr1a locus. In particular, V1aR expression in the retrosplenial cortex, a region of the brain that is critical in social cognition, is correlated with a single-nucleotide polymorphism (SNP) in the intron of the gene, implying that this region of the gene is significant in the regulation of avpr1a expression. The aim of this study was to develop an in vivo method to link genetic variation to variation in neuronal and behavioral phenotypes, and to apply the assay to the prairie vole model system. This was done by adapting the haploChIP method, which compares the expression of two alleles in heterozygous cells by using binding affinity to RNA Polymerase II as a marker for gene transcription. Chromatin immunoprecipitation targeting RNA Polymerase II did not demonstrate significant differences in binding between the two alleles for the avpr1a SNP. Preliminary results for a more specific marker of active transcription, Serine-2 Phosphorylated RNA Polymerase II, shows more promise in establishing a relationship between avpr1a intron variation and V1aR expression in the retrosplenial cortex. Further study, therefore, may reveal an important regulatory role for the avpr1a intron and thus provide insight into the complex processes that underlie social interactions.