Distinct transcriptional programs define a heterogeneous neuronal ensemble for social interaction.

Social interactions are encoded by the coordinated activity of heterogeneous cell types within distributed brain regions including the medial prefrontal cortex (mPFC). However, our understanding of the cell types which comprise the social ensemble has been limited by available mouse lines and reliance on single marker genes. We identified differentially active neuronal populations during social interactions by quantifying immediate-early gene (IEG) expression using snRNA-sequencing. These studies revealed that distinct prefrontal neuron populations composed of heterogeneous cell types are activated by social interaction. Evaluation of IEG expression within these recruited neuronal populations revealed cell-type and region-specific programs, suggesting that reliance on a single molecular marker is insufficient to quantify activation across all cell types. Our findings provide a comprehensive description of cell-type specific transcriptional programs invoked by social interactions and reveal insights into the neuronal populations which compose the social ensemble.