Deconstructing the neural circuit underlying social hierarchy in mice.

Social competition determines hierarchical social status, which profoundly influences animals' behavior and health. The dorsomedial prefrontal cortex (dmPFC) plays a fundamental role in regulating social competitions, but it was unclear how the dmPFC orchestrates win- and lose-related behaviors through its downstream neural circuits. Here, through whole-brain c-Fos mapping, fiber photometry, and optogenetics- or chemogenetics-based manipulations, we identified anatomically segregated win- and lose-related neural pathways downstream of the dmPFC in mice. Specifically, layer 5 neurons projecting to the dorsal raphe nucleus (DRN) and periaqueductal gray (PAG) promote social competition, whereas layer 2/3 neurons projecting to the anterior basolateral amygdala (aBLA) suppress competition. These two neuronal populations show opposite changes in activity during effortful pushes in competition. In vivo and in vitro electrophysiology recordings revealed inhibition from the lose-related pathway to the win-related pathway. Such antagonistic interplay may represent a central principle in how the mPFC orchestrates complex behaviors through top-down control.