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.

The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain–induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)–projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain–induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

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Parental behaviors are necessary for the development of mammalian infants. The medial preoptic area (MPOA) is thought to be the most important region for parental behaviors because lesions, cell-type specific ablation, and inactivation of the MPOA disrupt parental behaviors. Tracing studies reveal that the MPOA receives inputs from multiple brain regions including the amygdala, hypothalamus, and cortex. Among them, we focused on the amygdalohippocampal area (AHi), a brain region that contains MPOA-projecting neurons and expresses oxytocin receptors, which have been shown by genetic mutation and pharmacological studies to play crucial roles in social behaviors. However, little is known about the function of AHi-MPOA projection and the role of the intra-AHi oxytocin receptors in social behaviors. In this study, we found that MPOA-projection AHi neurons were activated by the social contact with pups. The electrophysiological experiments revealed that oxytocin enhanced inhibitory inputs to these neurons. Interestingly, this effect of oxytocin was potentiated in the paternal mice, which had experienced mating and parenting, compared with that in the virgin mice. Finally, chemogenetic activation of MPOA-projection AHi neurons with Gq-DREADD disrupted the expression of parental behaviors.In conclusion, the current study demonstrated the presence of input from the AHi to the MPOA that promotes male's behavior choice toward aggression. Oxytocin could reduce the tone of MPOA-projection AHi neurons, which suppress pup-directed aggression.