The authors describe cortical projections mediating the modulation of social behavior. Neural projections from the medial prefrontal cortex to the dorsal periaqueductal gray play a critical role in the behavioral adaptation to social defeat in mice. The prefrontal cortex helps adjust an organism's behavior to its environment. In particular, numerous studies have implicated the prefrontal cortex in the control of social behavior, but the neural circuits that mediate these effects remain unknown. Here we investigated behavioral adaptation to social defeat in mice and uncovered a critical contribution of neural projections from the medial prefrontal cortex to the dorsal periaqueductal gray, a brainstem area vital for defensive responses. Social defeat caused a weakening of functional connectivity between these two areas, and selective inhibition of these projections mimicked the behavioral effects of social defeat. These findings define a specific neural projection by which the prefrontal cortex can control and adapt social behavior.

Papale A, Morella IM, Indrigo MT, Bernardi RE, Marrone L, Marchisella F, Brancale A, Spanagel R, Brambilla R, Fasano S. 2016. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors. eLife 5:e17111. doi: 10.7554/eLife.17111.