Article | Published:

Functional identification of an aggression locus in the mouse hypothalamus

Nature volume 470, pages 221226 (10 February 2011) | Download Citation

Abstract

Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.

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Acknowledgements

We thank S. Ciocchi, S. Lin, Y. Ben-Shaul and A. Wang for advice on electrode and microdrive design; M. Gerfen and M. Vondrus for microdrive fabrication; M. P. Walsh, T. D. Heitzman and V. Rush for electronics support; A. Steele, R. Robbins, S. Ossorio, K. Gunapala, A. Paul, D. Oh, C. Kim and J. Nishiguchi for behaviour annotation and video scoring; H. Kim for technical assistance; W. E. Haubensak for teaching fibre-optic implant methods; J. T. Henderson for advice on stereotactic surgery; M. Kruk for advice on electrical stimulation experiments; K. Deisseroth for the Cre-dependent ChR2–EYFP AAV construct. M. Kruk, R. Mooney and R. Simerly for comments on the manuscripts; G. Mosconi for lab management and G. Mancuso for administrative support. This work was supported in part by the Weston-Havens Foundation and Jane Coffin Childs Foundation. D.J.A. is an Investigator of the Howard Hughes Medical Institute.

Author information

Affiliations

  1. Division of Biology 216-76, California Institute of Technology, 1201 East California Boulevard, Pasadena, California 91125, USA

    • Dayu Lin
    • , Hyosang Lee
    •  & David J. Anderson
  2. Howard Hughes Medical Institute, California Institute of Technology, 1201 East California Boulevard, Pasadena, California 91125, USA

    • Dayu Lin
    •  & David J. Anderson
  3. Allen Institute for Brain Science, Seattle, Washington, 98103, USA

    • Maureen P. Boyle
    •  & E. S. Lein
  4. Computation and Neural Systems 136-93, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA

    • Piotr Dollar
    •  & Pietro Perona

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Contributions

D.L. designed, carried out and analyzed preliminary fos catFISH experiments and all other experiments, and co-wrote the manuscript; M.B. and E.L. performed additional fos catFISH experiments; P.D. and P.P. developed custom behaviour annotation software; H.L. performed some of the optogenetic experiments; D.J.A. conceived the project, suggested experiments, analysed data and co-wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Dayu Lin or David J. Anderson.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    The file contains Supplementary Figures 1-19 with legends, Supplementary Methods, Supplementary Footnotes 1-4 and additional references.

Videos

  1. 1.

    Supplementary Movie 1

    The sound in this movie corresponds to the response of a neuron recorded from a C57BL/6 male during investigation and attack of a BALB/c male. Viewers are kindly requested not to upload this movie to other publicly accessible sites.

  2. 2.

    Supplementary Movie 2

    The sound in this movie corresponds to the response of the same neuron shown in Supplementary Movie 1 during investigation and mounting of a C57BL/6 female. Viewers are kindly requested not to upload this movie to other publicly accessible sites.

  3. 3.

    Supplementary Movie 3

    The movie shows an attack towards a BALB/c female is induced by light stimulation of a C57BL/6 male mouse in the VMHvl region. Viewers are kindly requested not to upload this movie to other publicly accessible sites.

  4. 4.

    Supplementary Movie 4

    The movie shows an attack towards a glove, which is induced by stimulating VMHvl in a C57BL/6 male mouse. Viewers are kindly requested not to upload this movie to other publicly accessible sites.

About this article

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DOI

https://doi.org/10.1038/nature09736

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