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.

中文翻译：

---

通过犁鼻器受体触发的边缘回路进行性排斥。

需要保护后代资源来平衡交配动力，但对交配负调控的神经基础仍然知之甚少。在啮齿动物中，信息素严格控制性行为。在这里，我们观察到外分泌腺分泌肽22（ESP22）（一种来自幼年小鼠的泪液蛋白）对小鼠成年女性性行为的抑制作用。ESP22激活专用的犁鼻器受体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关键的边缘系统连接，该连接抑制了生殖行为。此外，V2Rp4抵消了高度相关的犁鼻受体V2Rp5，该受体检测到男性信息素ESP1。有趣的是，V2Rp4和V2Rp5由相邻基因编码，却耦合到不同的回路，并介导对女性性行为的相反影响。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，更广泛地讲，输入是如何通过嗅觉回路传导引起特定行为的。