Single nucleus RNA-sequencing reveals transcriptional synchrony across different relationships

Relationships are shaped by reciprocal interaction and feedback between individuals. As relationships mature, pairs share common goals, improve their ability to work together, and experience coordinated emotions. However, the neural underpinnings responsible for this unique, pair-specific experience remain largely unexplored. Here, we used single nucleus RNA-sequencing to examine the transcriptional landscape of the nucleus accumbens (NAc) in socially monogamous prairie voles in long-term peer or mating-based relationships. We identified cell type-specific transcriptional differences between relationship types, including proportional differences in subpopulations of medium spiny neurons and module-based gene expression differences in interneurons. We also identified five gene modules correlated with different facets of social preference behavior. Finally, we show that, regardless of relationship type, prairie vole pairs exhibit transcription-based synchrony at the level of individual cells. Together, our results are consistent with a model in which a subset of gene expression changes promote relationship type-appropriate behaviors, while other non-overlapping gene expression changes support the social behaviors that are common across affiliative relationships. In addition, the similarity of gene expression observed across partners suggests an important role for the pair-specific social environment in shaping the NAc transcriptional landscape. This represents an emergent cellular property of social bonds that provides a potential biological mechanism by which shared social experience reinforces and strengthens relationships. ### Competing Interest Statement The authors declare the following competing interests: MAA and RDD have a patent for measuring transcription factor activity from eRNA activity. RD was a co-founder of Arpeggio Biosciences. All other authors have no competing interests.