Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, 113-8657, Japan.
Nat Commun. 2018 Oct 26;9(1):4463. doi: 10.1038/s41467-018-07003-5.
Mating drive is balanced by a need to safeguard resources for offspring, yet the neural basis for negative regulation of mating remains poorly understood. In rodents, pheromones critically regulate sexual behavior. Here, we observe suppression of adult female sexual behavior in mice by exocrine gland-secreting peptide 22 (ESP22), a lacrimal protein from juvenile mice. ESP22 activates a dedicated vomeronasal receptor, V2Rp4, and V2Rp4 knockout eliminates ESP22 effects on sexual behavior. Genetic tracing of ESP22-responsive neural circuits reveals a critical limbic system connection that inhibits reproductive behavior. Furthermore, V2Rp4 counteracts a highly related vomeronasal receptor, V2Rp5, that detects the male sex pheromone ESP1. Interestingly, V2Rp4 and V2Rp5 are encoded by adjacent genes, yet couple to distinct circuits and mediate opposing effects on female sexual behavior. Collectively, our study reveals molecular and neural mechanisms underlying pheromone-mediated sexual rejection, and more generally, how inputs are routed through olfactory circuits to evoke specific behaviors.
交配驱动力受到为后代保护资源的需求的平衡，但对于交配的负向调节的神经基础仍了解甚少。在啮齿动物中，信息素对性行为起着关键的调节作用。在这里，我们观察到外分泌腺分泌肽 22（ESP22）抑制成年雌性小鼠的性行为，ESP22 是来自幼鼠的一种泪蛋白。ESP22 激活了一种专门的犁鼻器受体 V2Rp4，而 V2Rp4 敲除消除了 ESP22 对性行为的影响。ESP22 反应性神经回路的遗传追踪揭示了一个关键的边缘系统连接，它抑制生殖行为。此外，V2Rp4 拮抗了一种高度相关的犁鼻器受体 V2Rp5，V2Rp5 检测到雄性信息素 ESP1。有趣的是，V2Rp4 和 V2Rp5 由相邻的基因编码，但偶联到不同的回路，并对雌性性行为产生相反的影响。总的来说，我们的研究揭示了信息素介导的性排斥的分子和神经机制，更普遍地揭示了输入如何通过嗅觉回路引发特定的行为。
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