Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States; Dominick P. Purpura Department of Neuroscience, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, United States
Zheng Wu
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States
Dominick P. Purpura Department of Neuroscience, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, United States
Victoria Sedwick
Dominick P. Purpura Department of Neuroscience, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, United States
Ming Tang
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States; FAS Informatics Group, Harvard University, Cambridge, United States
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.