Oxytocin Facilitates Allomaternal Behavior under Stress in Laboratory Mice
Oxytocin Facilitates Allomaternal Behavior under Stress in Laboratory Mice
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DOI：
10.1523/eneuro.0405-21.2022
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发表时间：
2022-01-01
期刊：
影响因子：
3.4
通讯作者：
Kuroda, Kumi O.
中科院分区：
文献类型：
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作者：
Tsuneoka, Yousuke;Yoshihara, Chihiro;Kuroda, Kumi O.
催产素（Oxt）控制生殖生理和各种社会行为，但Oxt对父母照顾的不同组成部分的确切贡献仍然需要确定。在这里，我们说明了父母养育诱导的神经元激活与大细胞Oxt神经元和纤维的内侧视前区（MPOA），父母和alloparent行为的关键大脑区域的神经解剖关系。我们使用基因靶向的小鼠品系Oxt，Oxt受体（Oxtr），加压素受体la（Avprla），加压素受体1b（Avp 1b）和促甲状腺激素释放激素（Trh）系统地研究Oxt相关信号传导在小狗定向行为中的作用。Oxtr-Avpr 1a-Avpr 1b三重基因敲除（TKO）和Oxt-Trh-Avpr 1a-Avpr 1b四重基因敲除（QKO）小鼠总体上健康且具有生育能力，除了它们的排乳完全缺乏和继发于母体Oxt或Oxtr基因丢失的分娩中度缺乏。在我们最小的压力条件下，TKO和QKO母亲和父亲，处女女性和男性的小狗定向行为基本上是无法区分的，从他们的同窝与其他基因型。然而，在束缚应激后立即进行的幼仔暴露试验中，Oxtr KO处女雌性确实显示出幼仔回收减少。Oxtr KO中的这种应激脆弱性被额外的Avpr 1b KO消除。一般的压力敏感性，测量血浆皮质醇升高后的约束压力或行为表现在开放领域（OF）和高架十字迷宫（ESTA），并没有改变在Oxtr KO，但减少了Avpr 1b KO女性，表明神经垂体激素的平衡影响的结果小狗导向的行为。
Oxytocin (Oxt) controls reproductive physiology and various kinds of social behaviors, but the exact contribution of Oxt to different components of parental care still needs to be determined. Here, we illustrate the neuroanatomical relations of the parental nurturing-induced neuronal activation with magnocellular Oxt neurons and fibers in the medial preoptic area (MPOA), the brain region critical for parental and alloparental behaviors. We used genetically-targeted mouse lines for Oxt, Oxt receptor (Oxtr), vasopressin receptor la (Avprla), vasopressin receptor 1b (Avp1b), and thyrotropin-releasing hormone (Trh) to systematically examine the role of Oxt-related signaling in pup-directed behaviors. The Oxtr-Avpr1a-Avpr1b triple knock-out (TKO), and Oxt-Trh-Avpr1a-Avpr1b quadruple KO (QKO) mice were grossly healthy and fertile, except for their complete deficiency in milk ejection and modest deficiency in parturition secondary to maternal loss of the Oxt or Oxtr gene. In our minimal stress conditions, pup-directed behaviors in TKO and QKO mothers and fathers, virgin females and males were essentially indistinguishable from those of their littermates with other genotypes. However, Oxtr KO virgin females did show decreased pup retrieval in the pup-exposure assay performed right after restraint stress. This stress vulnerability in the Oxtr KO was abolished by the additional Avpr1b KO. The general stress sensitivity, as measured by plasma cortisol elevation after restraint stress or by the behavioral performance in the open field (OF) and elevated plus maze (EPM), were not altered in the Oxtr KO but were reduced in the Avpr1b KO females, indicating that the balance of neurohypophysial hormones affects the outcome of pup-directed behaviors.