Two Preputial Gland-Secreted Pheromones Evoke Sexually Dimorphic Neural Pathways in the Mouse Vomeronasal System

Two Preputial Gland-Secreted Pheromones Evoke Sexually Dimorphic Neural Pathways in the Mouse Vomeronasal System
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两种包皮腺分泌的信息素在小鼠犁鼻系统中引起性别二态性神经通路

DOI:
10.3389/fncel.2019.00455
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发表时间:
2019-10-02
影响因子:
5.3
通讯作者:
Huang, Liquan
Huang, Liquan
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Qun;Zhang, Yaohua;Huang, Liquan

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十六醇(16 OH)和十六醇乙酸酯(16 Ac)是小鼠包皮腺分泌的两种大量信息素,对雌雄小鼠的作用不同。然而,潜在的分子和细胞机制仍有待阐明。在这项研究中,我们检查了这两种信息素对犁鼻感觉神经元(VSN)的激活,并绘制了处理和传递其化学信号的下游神经回路。利用钙离子显像和免疫组化方法,我们发现在雄性和雌性小鼠中,少数VSNs被16 OH、16 AC或两者激活,其中大多数位于犁鼻上皮的顶部,并且当16 OH和16 AC浓度增加10,000倍时,它们的数量并没有增加,除了雌性VSNs对16 OH有反应。在副嗅球(AOB)中,两种信息素诱发的前AOB(aAOB)区c-Fos+神经元数量多于后AOB(pAOB)区,且aAOB和pAOB区c-Fos+神经元数量的增加具有剂量依赖性;在性别间,雌性AOB对16 OH的反应强于16 Ac,而雄性AOB的反应则相反。这种性别二态性在很大程度上保留在下游脑区,包括终纹床核(BNST),内侧杏仁核(MeA),后内侧皮质杏仁核(PMCo),内侧视前区(MPA),下丘脑腹内侧核(VMH)。两者合计,我们的数据表明,有一个V1 R受体16 OH,16 Ac,或两者兼而有之,这些受体的激活唤起性二态神经回路,指导不同的行为输出,并可能调制其他信息素诱导的反应。
Hexadecanol (16OH) and hexadecyl acetate (16Ac) are two pheromones secreted in a large quantity by mouse preputial glands and act on male and female mice differentially. Yet the underlying molecular and cellular mechanisms remain to be elucidated. In this study, we examined the activation of vomeronasal sensory neurons (VSNs) by these two pheromones and mapped the downstream neural circuits that process and relay their chemosignals. Using the calcium imaging method and immunohistochemistry, we found that a small number of VSNs were activated by 16OH, 16AC, or both in the male and female mice, most of which were located apically in the vomeronasal epithelium, and their numbers did not increase when the concentrations of 16OH and 16Ac were raised by 10,000-fold except that of female VSNs in response to 16OH. In the accessory olfactory bulb (AOB), the two pheromones evoked more c-Fos+ neurons in the anterior AOB (aAOB) than in the posterior AOB (pAOB); and the increases in the number of c-Fos+ neurons in both aAOB and pAOB were dose-dependent; and between sexes, the female AOB responded more strongly to 16OH than to 16Ac whereas the male AOB had the opposite response pattern. This sexual dimorphism was largely retained in the downstream brain regions, including the bed nucleus of the stria terminalis (BNST), the medial amygdaloid nucleus (MeA), the posteromedial cortical amygdaloid nucleus (PMCo), the medial preoptic area (MPA), and the ventromedial hypothalamic nucleus (VmH). Taken together, out data indicate that there is one V1r receptor each for 16OH, 16Ac, or both, and that activation of these receptors evokes sexually dimorphic neural circuits, directing different behavioral outputs and possibly modulating other pheromone-induced responses.