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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
-We have included information about the applicability of our findings in the broader context of parental behavior across species in both the introduction and in the conclusion. -We have included new data regarding the activation of PeFAUcn3 neurons in virgin males that do not commit infanticide in order to address the impact of physiological state compared to behavior on the role of this circuit node in infant-directed behavior. -We have expanded the discussion regarding our optogenetic results of inhibiting and activating the PeFAUcn3 neurons at the cell bodies and their projections to further expand on how our specific findings fit into the context of a parental behavior circuit. -We have included in the discussion reference to our pilot experiments in which we attempted to manipulate this circuit in mothers and fathers which was unsuccessful. This data is mentioned as part of the expanded discussion of our parental circuit model. -We have added new electrophysiological data for both the optogenetic and chemogenetic manipulations to illustrate that the in vivo manipulations were effective. -We have included new electrophysiological data on the impact of projection-specific manipulations and discovered that the AHi projection is the highest fidelity connection, and we have expanded the discussion on how this finding dovetails with our behavioral finding that manipulation of this projection has the biggest impact on infant-directed aggression.
Brain region abbreviations
- MPOA
- medial preoptic area
- VLPO
- ventrolateral preoptic area
- Pe
- periventricular nucleus
- LSv
- ventral lateral septum
- LSi
- intermediate lateral septum
- BNSTm
- medial bed nucleus stria terminalis
- PeFA
- perifornical area
- PVH
- paraventricular hypothalamus
- DMH
- dorsomedial hypothalamus
- VMH
- ventromedial hypothalamus
- AH
- anterior hypothalamus
- LH
- lateral hypothalamus
- PLH
- peduncular lateral hypothalamus
- ZI
- zona incerta
- MeAPD
- posterodorsal medial amygdala
- MeAPV
- posteroventral medial amygdala
- Arc
- arcuate nucleus
- PMv
- ventral premammillary nucleus
- ME
- median eminence
- PH
- posterior hypothalamus
- AHi
- amygdalohippocampal area.
Frequently mentioned genes
- Ucn3
- Urocortin-3
- Gal
- Galanin
- Oxt
- Oxytocin
- Avp
- Vasopressin
- Trh
- Thyrotropin releasing hormone
- Crh
- Corticotropin releasing hormone.
Electrophysiology
- sEPSC
- spontaneous excitatory post synaptic current
- eEPSC
- evoked post synaptic current.