Control of intermale aggression by medial prefrontal cortex activation in the mouse

PLoS One. 2014 Apr 16;9(4):e94657. doi: 10.1371/journal.pone.0094657. eCollection 2014.


Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / physiology*
  • Animals
  • Female
  • Light
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Microscopy, Fluorescence
  • Motor Activity / physiology*
  • Neurons / physiology*
  • Neurons / virology
  • Optogenetics / methods
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Prefrontal Cortex / virology


  • Luminescent Proteins

Grant support

This research was funded in part by KAKENHI (23683021), Research Foundation for Opto-Science and Technology (, Takeda Science Foundation ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.