Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression
- Albert Einstein College of Medicine, United States
- Columbia University, United States
- Harvard University, United States
- 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).
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Expression data from adult male mouse hypothalamusNCBI Gene Expression Omnibus, GSE161507.
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Expression data from adult male mouse hypothalamusNCBI Gene Expression Omnibus, GSE161552.
Article and author information
Author details
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
- 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
- Received: November 6, 2020
- Preprint posted: July 29, 2021 (view preprint)
- Accepted: August 19, 2021
- Accepted Manuscript published: August 23, 2021 (version 1)
- 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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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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