The activation of prefrontal cortical neurons in aggression--a double labeling study.

Violence is associated with prefrontal deficits in humans, suggesting that this brain area inhibits aggressiveness. Its role, however, remains controversial, as certain subdivisions of the prefrontal cortex become activated by fights in rodents. Disparate human findings also show that this area is acutely activated by aggression under certain conditions. We explored prefrontal neuronal activation patterns in resident rats exposed to psychosocial (sensory contact with the intruder) and aggressive encounters. Both psychosocial and aggressive encounters increased c-Fos activation in the prelimbic (PrL), anterior cingular (Cg1), agranular insular (AI), ventral (VO) and lateral orbital (LO) cortices. The infralimbic (IL) and medial orbital (MO) cortices were activated significantly by aggressive encounters only. No other prefrontal regions were activated by psychosocial or aggressive encounters. The overwhelming majority of activated cells were pyramidal (glutamatergic) cells in the Cg1, IL, PrL, MO, and VO, whereas interneuron and pyramidal cell activation was similar in AI and LO. When rats showed violent aggression, the activation of GABAergic inhibitory cells decreased in these two, and two other areas (IL and MO). Notably, the latter two areas appeared to be specifically involved in aggressive behavior. The change occurred in a recently developed model of violent aggression. In this model, pyramidal cell activation in the above mentioned four areas (IL, MO, AI, and LO) predicted over 95% of variation in attack counts in general and violent attacks in particular. Based on these data, we present a tentative hypothesis on the involvement of the prefrontal cortex in the control of aggression.