Perifornical Area Urocortin-3 Neurons Promote Infant-directed Neglect and Aggression

Mammals invest considerable resources in protecting and nurturing young offspring. However, under certain physiological and environmental conditions, animals neglect or attack young conspecifics. Males in some species attack unfamiliar infants to gain reproductive advantage and females kill or neglect their young during stressful circumstances such as food shortage or threat of predation. In humans, stress is a risk factor in both sexes for peripartum disorders and associated impairments in parent-infant interactions. While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed neglect and aggression and the relationship between these behaviours and stress are poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the perifornical area (PeFAUcn3) of the hypothalamus are activated during infant-directed attacks in males and females, but not other forms of aggression. Opto- and chemogenetic manipulations of PeFAUcn3 neurons demonstrate the role of this neuronal population in the negative control of parenting in both males and females. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send major projections to the ventromedial hypothalamus (VMH), ventral lateral septum (LSv) and amygdalohippocampal area (AHi). Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers different aspects of infant-directed agonistic responses, such as neglect and aggression. Thus, PeFAUcn3 neurons emerge as a critical hub for the expression of infant-directed neglect and aggression, providing a new framework to examine the positive and negative regulation of parenting.