Sexual rejection via a vomeronasal receptor-triggered limbic circuit

Takuya Osakada, Kentaro K. Ishii, Hiromi Mori, Ryo Eguchi, David M. Ferrero, Yoshihiro Yoshihara, Stephen D. Liberles, Kazunari Miyamichi () and Kazushige Touhara ()
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Takuya Osakada: The University of Tokyo
Kentaro K. Ishii: The University of Tokyo
Hiromi Mori: The University of Tokyo
Ryo Eguchi: The University of Tokyo
David M. Ferrero: Harvard Medical School
Yoshihiro Yoshihara: ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo
Stephen D. Liberles: Harvard Medical School
Kazunari Miyamichi: The University of Tokyo
Kazushige Touhara: The University of Tokyo

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07003-5

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