TY - JOUR
T1 - Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression
AU - Autry, Anita E.
AU - Wu, Zheng
AU - Kapoor, Vikrant
AU - Kohl, Johannes
AU - Bambah-Mukku, Dhananjay
AU - Rubinstein, Nimrod D.
AU - Marin-Rodriguez, Brenda
AU - Carta, Ilaria
AU - Sedwick, Victoria
AU - Tang, Ming
AU - Dulac, Catherine
N1 - Funding Information:
This work was supported by a NIH K99 and R00 Award (K99HD085188, R00HD085188) and a
Funding Information:
We thank S. Sullivan for help with behavior scoring and mouse husbandry, and R. Hellmiss at MCB Graphics for work on illustrations. We thank members of the Dulac lab for comments on the manuscript, A. Leonard, E. Owolo, and L. Moussalime for assistance with data collection. This work was supported by a NIH K99 and R00 Award (K99HD085188, R00HD085188) and a NARSAD Young Investigator award to A.E.A., a Human Frontier Long-Term Fellowship, a European Molecular Biology Organization Long-Term Fellowship (ALTF 1008-2014) and a Sir Henry Wellcome Fellowship from the Wellcome Trust to J.K., a NIH K99 Award (K99HD092542) to D.J.B.M, a Howard Hughes Gilliam Fellowship for Advanced Study to B.M.B., and NIH grant 1R01HD082131-01A1 to C.D. C. D. is an investigator of the Howard Hughes Medical Institute.
Funding Information:
Henry Wellcome Fellowship from the Wellcome Trust to J.K., a NIH K99 Award (K99HD092542)
Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.64680
DO - 10.7554/eLife.64680
M3 - Article
C2 - 34423776
AN - SCOPUS:85114431045
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
M1 - e64680
ER -