Transcriptomic regulations underlying pair-bond formation and maintenance in the socially monogamous male and female prairie vole

Abstract Background The ability to form enduring social bonds is characteristic of human nature and impairments in social affiliation are central features of severe neuropsychiatric disorders including autism spectrum disorders and schizophrenia. Due to its ability to form long-term pair-bonds, the socially monogamous prairie vole has emerged as an excellent model to study the neurobiology of social attachment. Despite the enduring nature of the bond, however, surprisingly few genes have been implicated in the pair-bonding process in either sex. Methods Male and female prairie voles (Microtus ochrogaster) were cohabitated with an opposite-sex partner for 24 hrs or 3 weeks (3W) and transcriptomic regulations in the nucleus accumbens (NAc) were measured by RNA-sequencing. Results We found sex-specific response patterns despite similar behavioral indicators of pair-bond establishment. Indeed, 24 hrs of cohabitation with an opposite-sex partner induced widespread transcriptomic changes that remained sustained to some extent in females after 3W but returned to baseline before a second set of regulations in males. This led to a highly sexually-biased NAc transcriptome at 3W related to processes such as neurotransmission, protein turnover, and DNA transcription. In particular, we found sex-specific alterations of mitochondrial dynamics following cohabitation, with a shift towards fission in males. Conclusions In addition to identifying the genes, networks, and pathways involved in the pair-bonding process in the NAc, our work illustrates the vast extent of sex differences in the molecular mechanisms underlying pair-bonding in prairie voles, and paves the way to further our understanding of the complex social bonding process.