Letter | Published:

Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex

Nature volume 550, pages 388392 (19 October 2017) | Download Citation


All animals possess a repertoire of innate (or instinctive1,2) behaviours, which can be performed without training. Whether such behaviours are mediated by anatomically distinct and/or genetically specified neural pathways remains unknown3,4,5. Here we report that neural representations within the mouse hypothalamus, that underlie innate social behaviours, are shaped by social experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting in rodents6,7,8. We used microendoscopy9 to image Esr1+ neuronal activity in the VMHvl of male mice engaged in these social behaviours. In sexually and socially experienced adult males, divergent and characteristic neural ensembles represented male versus female conspecifics. However, in inexperienced adult males, male and female intruders activated overlapping neuronal populations. Sex-specific neuronal ensembles gradually separated as the mice acquired social and sexual experience. In mice permitted to investigate but not to mount or attack conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual experience with a female was sufficient to promote the separation of male and female ensembles and to induce an attack response 24 h later. These observations uncover an unexpected social experience-dependent component to the formation of hypothalamic neural assemblies controlling innate social behaviours. More generally, they reveal plasticity and dynamic coding in an evolutionarily ancient deep subcortical structure that is traditionally viewed as a ‘hard-wired’ system.

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We thank X. Wang, J. S. Chang and R. Robertson for technical help, H. Lee and P. Kunwar for experimental advice, D. Senyuz for testing behaviour in wild-type mice, D.-W. Kim for pilot experiments, M. McCardle and C. Chiu for genotyping, J.Costanza for mouse colony management, G. Stuber for advice on GCaMP6s expression, Inscopix Inc. for technical support, P. Perona for mouse tracking software, L. Abbott for comments on the manuscript, R. Axel, D. Y. Tsao and M. Meister for critical feedback, X. Da and C. Chiu for laboratory management and G. Mancuso for Administrative Assistance. D.J.A. and M.J.S. are Investigators of the Howard Hughes Medical Institute and Paul G. Allen Distinguished Investigators. This work was supported in part by NIH grant no. R01MH070053, and grants from the Gordon Moore Foundation, Ellison Medical Research Foundation, Simons Foundation and Guggenheim Foundation to D.J.A. A.K. is a fellow of the Helen Hay Whitney Foundation, M.Z. is a recipient of fellowships from the NSF and L’Oréal USA Women in Science.

Author information

Author notes

    • Benjamin F. Grewe

    Present address: Institute of Neuroinformatics, ETH Zurich, CH-8057 Zurich, Switzerland.

    • Ryan Remedios
    •  & Ann Kennedy

    These authors contributed equally to this work.


  1. Division of Biology and Biological Engineering 156-29, Tianqiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, California 91125, USA

    • Ryan Remedios
    • , Ann Kennedy
    • , Moriel Zelikowsky
    •  & David J. Anderson
  2. James H. Clark Center for Biomedical Engineering & Sciences, Stanford University, Stanford, California 94305, USA

    • Benjamin F. Grewe
    •  & Mark J. Schnitzer
  3. CNC Program, Stanford University, Stanford, California 94305, USA

    • Benjamin F. Grewe
    •  & Mark J. Schnitzer
  4. Howard Hughes Medical Institute, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA

    • Mark J. Schnitzer
    •  & David J. Anderson


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R.R. designed and performed all imaging experiments, processed the data, contributed to analysis and co-wrote the manuscript; A.K. performed computational analysis, prepared figures and co-wrote the manuscript; M.Z. designed and performed behavioural experiments; M.J.S. and B.F.G. provided training for R.R., guidance on experimental design and data analysis, and critical feedback; D.J.A. supervised the project and co-wrote the manuscript.

Competing interests

M.J.S. is a scientific co-founder of Inscopix Inc., which produced the miniature fluorescence microscope used in this study. R.R., A.K., M.Z., B.F.G. and D.J.A. declare no competing financial interests.

Corresponding author

Correspondence to David J. Anderson.

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