In mammals, the development of healthy offspring requires maternal care. Behavior by lactating mothers toward other individuals is an important component of maternal aggression. However, it is unclear whether fathers display aggression primed by pups (an external factor), and the protection mechanism is poorly understood. To address this question, we examined paternal aggression in the ICR mouse strain. We found that sires exposed to cues from pups and lactating dams showed stronger aggression toward intruders than did sires that were deprived of family cues or exposed to nonlactating mates. c-Fos immunohistochemistry showed that cells in both the paraventricular and supraoptic nuclei (PVN and SON, respectively) in the hypothalamus of sires exposed to any cues were highly activated. However, c-Fos activation in oxytocinergic neurons was increased only in sires exposed to pup cues and solely in the PVN. In Cd38-knockout sires, the presence of pups induced no or reduced parental aggression; however, this phenotype was recovered, that is, aggression increased to the wild-type level, after intraperitoneal administration of oxytocin (OT). Specific c-Fos activation patterns induced by pup cues were not found in the PVN of knockout sires. These results demonstrate that the PVN is one of the primary hypothalamic areas involved in paternal aggression and suggest that a CD38-dependent OT mechanism in oxytocinergic neurons is critical for part of the behavior associated with the protection of offspring by nurturing male mice.

中文翻译：

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室旁核中的催产素和CD38在小鼠的父亲侵害中起关键作用。

在哺乳动物中，健康后代的发育需要母体护理。哺乳母亲对其他个体的行为是母体侵略的重要组成部分。然而，尚不清楚父亲是否表现出由幼崽（外部因素）引发的侵略，并且保护机制还知之甚少。为了解决这个问题，我们检查了ICR小鼠品系中的父亲攻击性。我们发现，暴露于幼崽和泌乳水坝线索的公羊比被剥夺家庭线索或暴露于不哺乳伴侣的公​​羊对入侵者的攻击性更强。c-Fos免疫组织化学显示，暴露于任何线索的母猪下丘脑室旁和视上核中的细胞（分别为PVN和SON）均被高度激活。然而，催产素能神经元中的c-Fos激活仅在暴露于幼仔线索的父系中和仅在PVN中增加。在Cd38基因敲除的公母中，幼崽的存在不会引起父母的攻击或父母的攻击不会减少。然而，腹膜内施用催产素（OT）后，该表型得以恢复，即攻击性增加至野生型水平。在敲除父亲的PVN中未发现幼虫线索诱导的特定c-Fos激活模式。这些结果表明，PVN是参与父系攻击的主要下丘脑区域之一，并表明催产素能神经元中CD38依赖的OT机制对于与通过养育雄性小鼠保护后代有关的部分行为至关重要。幼崽的存在不会引起父母的攻击或父母的攻击不会减少；然而，腹膜内施用催产素（OT）后，该表型得以恢复，即攻击性增加至野生型水平。在敲除父亲的PVN中未发现幼虫线索诱导的特定c-Fos激活模式。这些结果表明，PVN是参与父系攻击的主要下丘脑区域之一，并表明催产素能神经元中CD38依赖的OT机制对于与通过养育雄性小鼠保护后代有关的部分行为至关重要。幼崽的存在不会引起父母的攻击或父母的攻击不会减少；然而，腹膜内施用催产素（OT）后，该表型得以恢复，即攻击性增加至野生型水平。在敲除父亲的PVN中未发现幼虫线索诱导的特定c-Fos激活模式。这些结果表明，PVN是参与父系攻击的主要下丘脑区域之一，并表明催产素能神经元中CD38依赖的OT机制对于与通过养育雄性小鼠保护后代有关的部分行为至关重要。在敲除父亲的PVN中未发现幼虫线索诱导的特定c-Fos激活模式。这些结果表明，PVN是参与父系攻击的主要下丘脑区域之一，并表明催产素能神经元中CD38依赖的OT机制对于与通过养育雄性小鼠保护后代有关的部分行为至关重要。在敲除父亲的PVN中未发现幼虫线索诱导的特定c-Fos激活模式。这些结果表明，PVN是参与父系攻击的主要下丘脑区域之一，并表明催产素能神经元中CD38依赖的OT机制对于与通过养育雄性小鼠保护后代有关的部分行为至关重要。