A circuit from hippocampal CA2 to lateral septum disinhibits social aggression

Nature. 2018 Dec;564(7735):213-218. doi: 10.1038/s41586-018-0772-0. Epub 2018 Dec 5.


Although the hippocampus is known to be important for declarative memory, it is less clear how hippocampal output regulates motivated behaviours, such as social aggression. Here we report that pyramidal neurons in the CA2 region of the hippocampus, which are important for social memory, promote social aggression in mice. This action depends on output from CA2 to the lateral septum, which is selectively enhanced immediately before an attack. Activation of the lateral septum by CA2 recruits a circuit that disinhibits a subnucleus of the ventromedial hypothalamus that is known to trigger attack. The social hormone arginine vasopressin enhances social aggression by acting on arginine vasopressin 1b receptors on CA2 presynaptic terminals in the lateral septum to facilitate excitatory synaptic transmission. In this manner, release of arginine vasopressin in the lateral septum, driven by an animal's internal state, may serve as a modulatory control that determines whether CA2 activity leads to declarative memory of a social encounter and/or promotes motivated social aggression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / physiology*
  • Animals
  • Arginine Vasopressin / metabolism
  • CA2 Region, Hippocampal / cytology*
  • CA2 Region, Hippocampal / physiology*
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Excitatory Postsynaptic Potentials
  • Female
  • Male
  • Memory / physiology
  • Mice
  • Mice, Inbred BALB C
  • Motivation
  • Neural Inhibition*
  • Neural Pathways / physiology*
  • Presynaptic Terminals / metabolism
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Pyramidal Cells / metabolism
  • Receptors, Vasopressin / metabolism
  • Septal Nuclei / cytology*
  • Septal Nuclei / physiology*
  • Social Behavior*
  • Synaptic Transmission
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / physiology


  • Proto-Oncogene Proteins c-fos
  • Receptors, Vasopressin
  • arginine vasopressin receptor 1b, mouse
  • Arginine Vasopressin
  • Clozapine
  • clozapine N-oxide