The journal of neuroscience : the official journal of the Society for Neuroscience.

The Temporal Association Cortex Plays a Key Role in Auditory-Driven Maternal Plasticity.

Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.SIGNIFICANCE STATEMENT The medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.

https://www.jneurosci.org/content/jneuro/40/20/3981.full.pdf

Amygdalohippocampal Area Neurons That Project to the Preoptic Area Mediate Infant-Directed Attack in Male Mice.

Plasticity of neural connections underlying oxytocin-mediated parental behaviors of male mice

Parenting — a paradigm for investigating the neural circuit basis of behavior

SUMMARY 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 advantage1–3 and females kill or neglect their young during stressful circumstances such as food shortage or threat of predation4–8. In humans, stress is a risk factor in both sexes for peripartum disorders and associated impairments in parent-infant interactions9. While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting10–13, 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.

/pdf/perifornical-area-urocortin-3-neurons-promote-infant-46fauwpnw8.pdf

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

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.

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

/pdf/author-response-urocortin-3-neurons-in-the-mouse-461ndwc9mr.pdf

Victoria Sedwick

Papers

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

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

Author response: Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression