Article | Published:

Hypothalamic control of male aggression-seeking behavior

Nature Neuroscience volume 19, pages 596604 (2016) | Download Citation

Abstract

In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.

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Acknowledgements

The authors thank A. Song, A. Chow, N. Cuvelier, K. Fergusen, C. Heins and K. Liu for assistance with behavioral training and video annotation, T. Akay for EMG guidance, L. Wang for genotyping, B. Roth (University of North Carolina) for providing the AAV Syn::DIO-DREADDi-mCherry construct, the Genetically-Encoded Neuronal Indicator and Effector (GENIE) Project and the Janelia Farm Research Campus of the Howard Hughes Medical Institute for GCamP6 construct, G. Cui for advice on fiber photometry, J. LeDoux, K. Hashikawa, M. Long, K. Kuchibhotla, A. Fink, C. Schoonover and M. Goldberg for helpful discussions, and P. Hare for editorial comments. This work was supported by the Esther A. & Joseph Klingenstein Fund (D.L.), the Whitehall Foundation (D.L.), the Sloan Foundation (D.L.), the McKnight Foundation (D.L.), and a grant from the US National Institutes of Health (1R01MH101377) (D.L.).

Author information

Affiliations

  1. Institute of Neuroscience, New York University School of Medicine, New York, New York, USA.

    • Annegret L Falkner
    •  & Dayu Lin
  2. Department of Bioengineering, Neuroscience Program, Stanford University, Stanford, California, USA.

    • Logan Grosenick
    •  & Karl Deisseroth
  3. Department of Bioengineering and CNC Program, Stanford University, Stanford, California, USA.

    • Thomas J Davidson
  4. Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.

    • Karl Deisseroth
  5. Department of Psychiatry, New York University School of Medicine, New York, New York, USA.

    • Dayu Lin
  6. Center for Neural Science, New York University, New York, New York, USA.

    • Dayu Lin

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Contributions

D.L. and A.L.F. conceived the project, designed the experiments, interpreted the results and wrote the paper. A.L.F. performed all of the experiments and analyzed the data. L.G., T.J.D. and K.D. contributed to the development and improvement of the fiber photometry technique.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Annegret L Falkner or Dayu Lin.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–9

  2. 2.

    Supplementary Methods Checklist

Videos

  1. 1.

    Example early and late training self-initiated aggression trials with associated GCaMP6 response in the VMHvl.

    Whereas the response during the early training trial is flat at the time of the nosepoke (the seeking epoch), the response during the late training trial shows increases as the animal nosepokes and waits for the introduction of the male. In both trials, the response increases during the interaction phase following the male introduction.

  2. 2.

    Optogenetic activation of the VMHvl promotes short latency trial initiation during the self-initiated aggression task.

    A fully task trained animal with ChR2 expression in the VMHvl performs the SIA task. No poking occurs during a 10 min sham stimulation (0 mW). After this sham stimulation trial, VMHvl stimulation begins (10 ms, 5 Hz, 1 mW), and the animal pokes the social port quickly and attacks the submissive male upon its introduction.

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DOI

https://doi.org/10.1038/nn.4264

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