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Nat Commun

Title:		Sexual rejection via a vomeronasal receptor-triggered limbic circuit
Author(s):		Osakada T; Ishii KK; Mori H; Eguchi R; Ferrero DM; Yoshihara Y; Liberles SD; Miyamichi K; Touhara K;
Address:		"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. Department of Cell Biology, Harvard Medical School, Boston, 02115, Massachusetts, USA. RIKEN Center for Brain Science, Saitama, 351-0198, Japan. Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan. kazunari.miyamichi@riken.jp. ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, 113-8657, Japan. kazunari.miyamichi@riken.jp. RIKEN Center for Biosystems Dynamics Research, Hyogo, 650-0047, Japan. kazunari.miyamichi@riken.jp. Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan. ktouhara@mail.ecc.u-tokyo.ac.jp. ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, 113-8657, Japan. ktouhara@mail.ecc.u-tokyo.ac.jp. International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, Tokyo, 113-0033, Japan. ktouhara@mail.ecc.u-tokyo.ac.jp"
Journal Title:		Nat Commun
Year:		2018
Volume:		20181026
Issue:		1
Page Number:		4463 -
DOI:		10.1038/s41467-018-07003-5
ISSN/ISBN:		2041-1723 (Electronic) 2041-1723 (Linking)
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"
Keywords:		"Animals Female Lacrimal Apparatus/metabolism Limbic System/cytology/*metabolism Male Mice Mice, Inbred C3H Mice, Inbred C57BL Neurons/metabolism Pheromones/*metabolism/pharmacology Proto-Oncogene Proteins c-fos/analysis/metabolism Receptors, Pheromone/def;"
Notes:		"MedlineOsakada, Takuya Ishii, Kentaro K Mori, Hiromi Eguchi, Ryo Ferrero, David M Yoshihara, Yoshihiro Liberles, Stephen D Miyamichi, Kazunari Touhara, Kazushige eng R01 DC013289/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2018/10/28 Nat Commun. 2018 Oct 26; 9(1):4463. doi: 10.1038/s41467-018-07003-5"