Single cell transcriptomic representation of social dominance in prefrontal cortex and the influence of preweaning maternal and postweaning social environment
Social dominance encompasses winning dyadic contests and gaining priority access to resources and reproduction. Disposition to dominance is influenced by environmental factors, particularly during early postnatal life and adolescence. A disinhibitory mPFC microcircuit has been implicated in the expression of dominance in the “tube test” paradigm of social competition in mice, but the neuronal and transcriptional plasticity associated with the environment induced increase in social dominance is not known. We previously reported that male pups raised by physically active (as opposed to sedentary) dams exhibit dominance and increased reproductive fitness, and here we show that social isolation from weaning also increases dominance. By using these preweaning and postweaning environmental models, we tested if dominance is associated with transcriptional plasticity and a specific transcriptional profile in one or more cell types in the mPFC. Given that the mPFC is composed of several cell types, we used single cell transcriptomics to characterize the influence of the preweaning maternal and postweaning social environment on cell-type specific gene expression. The preweaning maternal effect, but not postweaning social isolation, caused gene expression changes in a wide range of cell types including pyramidal neurons, various interneurons, and astrocytes. However, both the maternal effect and social isolation induced the coordinated downregulation of synaptic channel, receptor, and adhesion genes in parvalbumin positive (PV) interneurons. This suggests an impaired PV interneuron-mediated inhibition of pyramidal cells in animals predisposed to dominance, a notion consistent with dominant behavior being driven by the disinhibition of mPFC pyramidal neurons. Overall design: PL of mPFC was dissected at P21 from C57BL/6 mice. Cohort 1 has 2 groups (GH Run, GH Sed). Cohort 2 has 4 groups (GH Run, GH Sed, SI Run, SI Sed)