Hippocampal-hypothalamic circuit controls context-dependent innate defensive responses

  1. Jee Yoon Bang
  2. Julia Kathryn Sunstrum
  3. Danielle Garand
  4. Gustavo Morrone Parfitt
  5. Melanie Woodin
  6. Wataru Inoue
  7. Junchul Kim  Is a corresponding author
  1. University of Toronto, Canada
  2. Western University, Canada
  3. Icahn School of Medicine at Mount Sinai, United States

Abstract

Preys use their memory - where they sensed a predatory threat and whether a safe shelter is nearby - to dynamically control their survival instinct to avoid harm and reach safety. However, it remains unknown which brain regions are involved, and how such top-down control of innate behaviour is implemented at the circuit level. Here, using adult male mice, we show that the anterior hypothalamic nucleus (AHN) is best positioned to control this task as an exclusive target of the hippocampus (HPC) within the medial hypothalamic defense system. Selective optogenetic stimulation and inhibition of hippocampal inputs to the AHN revealed that the HPC→AHN pathway not only mediates the contextual memory of predator threats but also controls the goal-directed escape by transmitting information about the surrounding environment. These results reveal a new mechanism for experience-dependent, top-down control of innate defensive behaviours.

Data availability

Numerical data used to generate Figures 1-8 and Extended data figures 1-12 are provided in the Figure Source Data files that correspond to figure labels. Custom written MATLAB code is uploaded on Zenodo. (10.5281/zenodo.5899428)

Article and author information

Author details

  1. Jee Yoon Bang

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Julia Kathryn Sunstrum

    Robarts Research Institute, Western University, London, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Danielle Garand

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Gustavo Morrone Parfitt

    Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0168-4099
  5. Melanie Woodin

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2984-8630
  6. Wataru Inoue

    Robarts Research Institute, Western University, London, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2438-5123
  7. Junchul Kim

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    For correspondence
    junchul.kim@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9920-3307

Funding

Canadian Institute of Health Research (507489)

  • Junchul Kim

NSERC Discovery (506730)

  • Junchul Kim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mario Penzo, National Institute of Mental Health, United States

Ethics

Animal experimentation: All procedures were approved by the Local Animal Care Committee (LACC) at University of Toronto. AUP2011332.

Version history

  1. Preprint posted: August 9, 2021 (view preprint)
  2. Received: October 15, 2021
  3. Accepted: April 13, 2022
  4. Accepted Manuscript published: April 14, 2022 (version 1)
  5. Version of Record published: April 26, 2022 (version 2)
  6. Version of Record updated: May 9, 2022 (version 3)

Copyright

© 2022, Bang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jee Yoon Bang
  2. Julia Kathryn Sunstrum
  3. Danielle Garand
  4. Gustavo Morrone Parfitt
  5. Melanie Woodin
  6. Wataru Inoue
  7. Junchul Kim
(2022)
Hippocampal-hypothalamic circuit controls context-dependent innate defensive responses
eLife 11:e74736.
https://doi.org/10.7554/eLife.74736

Share this article

https://doi.org/10.7554/eLife.74736

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