Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression

  1. Anita E Autry
  2. Zheng Wu
  3. Vikrant Kapoor
  4. Johannes Kohl
  5. Dhananjay Bambah-Mukku
  6. Nimrod D Rubinstein
  7. Brenda Marin-Rodriguez
  8. Ilaria Carta
  9. Victoria Sedwick
  10. Ming Tang
  11. Catherine Dulac  Is a corresponding author
  1. Albert Einstein College of Medicine, United States
  2. Columbia University, United States
  3. Harvard University, United States
  4. The Francis Crick Institute, United Kingdom

Abstract

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

Data availability

- Microarray data have been deposited in GEO under accession code GSE161507 and analysis code can be found at https://gitlab.com/dulaclab/ucn3_neuron_microarray.- pS6 data have been deposited in GEO under accession code GSE161552 and analysis code is available on Github (https://gitlab.com/dulaclab/ucn3_neuron_microarray/-/tree/master/braimSourceCode/braim.R).

The following data sets were generated

Article and author information

Author details

  1. Anita E Autry

    Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    No competing interests declared.
  2. Zheng Wu

    Department of Neuroscience, Columbia University, New York, United States
    Competing interests
    No competing interests declared.
  3. Vikrant Kapoor

    Molecular and cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Johannes Kohl

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8222-0282
  5. Dhananjay Bambah-Mukku

    Molecular and cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  6. Nimrod D Rubinstein

    Molecular and cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  7. Brenda Marin-Rodriguez

    Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  8. Ilaria Carta

    Neuroscience, Albert Einstein College of Medicine, Bronx NY, United States
    Competing interests
    No competing interests declared.
  9. Victoria Sedwick

    Neuroscience, Albert Einstein College of Medicine, Bronx NY, United States
    Competing interests
    No competing interests declared.
  10. Ming Tang

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  11. Catherine Dulac

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    dulac@fas.harvard.edu
    Competing interests
    Catherine Dulac, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5024-5418

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD085188)

  • Anita E Autry

Brain and Behavior Research Foundation (NARSAD Young Investigator)

  • Anita E Autry

European Molecular Biology Laboratory (ALTF 1008-2014)

  • Johannes Kohl

Wellcome Trust (Sir Henry Wellcome Fellowship)

  • Johannes Kohl

National Institute of Mental Health (K99HD092542)

  • Dhananjay Bambah-Mukku

Eunice Kennedy Shriver National Institute of Child Health and Human Development (1R01HD082131-01A1)

  • Catherine Dulac

Howard Hughes Medical Institute (HHMI investigator)

  • Catherine Dulac

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

Reviewing Editor

  1. Mary Kay Lobo, University of Maryland, United States

Ethics

Animal experimentation: All animal experiments were approved by the Harvard University Institutional Animal Care and Use Committee. All experiments were performed in compliance with our Harvard University IACUC approved protocols 97-03-3, 23-12-3, and 25-13-3

Version history

  1. Received: November 6, 2020
  2. Preprint posted: July 29, 2021 (view preprint)
  3. Accepted: August 19, 2021
  4. Accepted Manuscript published: August 23, 2021 (version 1)
  5. Version of Record published: September 20, 2021 (version 2)

Copyright

© 2021, Autry 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. Anita E Autry
  2. Zheng Wu
  3. Vikrant Kapoor
  4. Johannes Kohl
  5. Dhananjay Bambah-Mukku
  6. Nimrod D Rubinstein
  7. Brenda Marin-Rodriguez
  8. Ilaria Carta
  9. Victoria Sedwick
  10. Ming Tang
  11. Catherine Dulac
(2021)
Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression
eLife 10:e64680.
https://doi.org/10.7554/eLife.64680

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https://doi.org/10.7554/eLife.64680