Distinct Roles for Prefrontal Dopamine D1 and D2 Neurons in Social Hierarchy

Abstract

Neuronal activity in the prefrontal cortex (PFC) controls dominance hierarchies in groups of animals. Dopamine (DA) strongly modulates PFC activity mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs). Still, it is unclear how these two subpopulations of DA receptor-expressing neurons in the PFC regulate social dominance hierarchy. Here, we demonstrate distinct roles for prefrontal D1R- and D2R-expressing neurons in establishing social hierarchy, with D1R1 neurons determining dominance and D2R1 neurons for subordinate. Ex vivo whole-cell recordings revealed that the dominant status of male mice correlates with rectifying AMPAR transmission and stronger excitatory synaptic strength onto D1R1 neurons in PFC pyramidal neurons. In contrast, the submissive status is associated with higher neuronal excitability in D2R1 neurons. Moreover, simultaneous manipulations of synaptic efficacy of D1R1 neurons in dominant male mice and neuronal excitability of D2R1 neurons of their male subordinates switch their dominant–subordinate relationship. These results reveal that prefrontal D1R1 and D2R1 neurons have distinct but synergistic functions in the dominance hierarchy, and DA-mediated regulation of synaptic strengths acts as a powerful behavioral determinant of intermale social rank.