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Sexual rejection via a vomeronasal receptor-triggered limbic circuit

Author

Listed:
  • Takuya Osakada

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo)

  • Kentaro K. Ishii

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo)

  • Hiromi Mori

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo)

  • Ryo Eguchi

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo)

  • David M. Ferrero

    (Harvard Medical School)

  • Yoshihiro Yoshihara

    (ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo
    RIKEN Center for Brain Science)

  • Stephen D. Liberles

    (Harvard Medical School)

  • Kazunari Miyamichi

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research)

  • Kazushige Touhara

    (The University of Tokyo
    ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo
    The University of Tokyo Institutes for Advanced Study)

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.

Suggested Citation

  • Takuya Osakada & Kentaro K. Ishii & Hiromi Mori & Ryo Eguchi & David M. Ferrero & Yoshihiro Yoshihara & Stephen D. Liberles & Kazunari Miyamichi & Kazushige Touhara, 2018. "Sexual rejection via a vomeronasal receptor-triggered limbic circuit," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07003-5
    DOI: 10.1038/s41467-018-07003-5
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