Functional demonstration of sexual signal neural circuits

• Project/Area Number: 15K14881
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: Azabu University
• Principal Investigator: Kikusui Takefumi 麻布大学, 獣医学部, 教授 (90302596)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: フェロモン / 性差 / 嗅覚 / 性行動 / マウス / ESP1 / ブルース効果 / 扁桃体 / 攻撃行動

Outline of Final Research Achievements

Male and female mice can recognize the conspecific sex information and show adaptive behavior to the counterpart. In this study, we aimed to reveal the functional differences in male and female brain conveying the sex-related signals. ESP1 is a male pheromone secreted into male tears. ESP1 stimulates female receptive behavior and enhances male aggression. We identified the nuclei that were activated by ESP1 both in male and females, using neural activity marker C-fos. By pharmacogenetics approach, we artificially activated these nuclei and were able to reproduce the female sexual behavior and male aggression. Therefore, we demonstrated the functional sex differences in the brain that regulating ESP1-related sex-specific behavior.

Research Products

• [Journal Article] Mutual mother-infant recognition in mice: the role of pup ultrasonic vocalizations (2017)
  • Author(s): Mogi K, Takakuda A, Tsukamoto C, Oyama R, Okabe S, Koshida N, Nagasawa M, Kikusui T.
  • Journal Title: Behav Brain Res. Volume: 325 Pages: 138-146
  • DOI: 10.1016/j.bbr.2016.08.044
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Self-Generated Environmental Factor as a Potential Contributor to Atypical Early Social Communication in Autism (2017)
  • Author(s): Kikusui T, Hiroi N
  • Journal Title: Neuropsychopharmacology. Volume: 42 Issue: 1 Pages: 378-378
  • DOI: 10.1038/npp.2016.225
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice (2017)
  • Author(s): Okabe, S., Tsuneoka, Y., Takahashi, A., Ooyama, R., Watarai, A., Maeda, S., Honda, Y., Nagasawa, M., Mogi, K., Nishimori, K., Kuroda, M., Koide, T., Kikusui, T.
  • Journal Title: Psychoneuroendocrinology Volume: 79 Pages: 20-30
  • DOI: 10.1016/j.psyneuen.2017.01.036
  • Peer Reviewed / Open Access
• [Journal Article] Nrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odor-induced attractive social responses (2017)
  • Author(s): Kasumi Inokuchi , Fumiaki Imamura , Haruki Takeuchi , Ryang Kim , Hiroyuki Okuno , Hirofumi Nishizumi , Haruhiko Bito, Takefumi Kikusui, Hitoshi Sakano
  • Journal Title: Nature Communication Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice (2016)
  • Author(s): Tatsuya Hattori, Takuya Osakada, Ayaka Matsumoto, Naoki Matsuo, Sachiko Haga-Yamanaka, Takaya Nishida, Yuji Mori, Kazutaka Mogi, Kazushige Touhara, Takefumi Kikusui
  • Journal Title: Current Biology Volume: 26 Issue: 9 Pages: 1229-1234
  • DOI: 10.1016/j.cub.2016.03.029
  • Peer Reviewed / Open Access
• [Journal Article] Structure and function of neonatal social communication in a genetic mouse model of autism. (2016)
  • Author(s): T. Takahashi, S. Okabe, P. Ó Broin, A. Nishi, K. Ye, M. V. Beckert, T. Izumi, A. Machida, G. Kang, Seiji Abe, J. L. Pena, A. Golden, T. Kikusui, N. Hiroi.
  • Journal Title: Molecular Psychiatry Volume: in press Issue: 9 Pages: 1-7
  • DOI: 10.1038/mp.2015.190
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 内分泌を社会から考える (2015)
  • Author(s): 菊水健史
  • Organizer: 神経内分泌学会
  • Place of Presentation: 東北大学
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] フェロモン伝達系の性差 (2015)
  • Author(s): 服部達哉、菊水健史
  • Organizer: 神経内分泌学会
  • Place of Presentation: 東北大学
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] Oxytocin forms inter-individual relationship (2015)
  • Author(s): Takefumi Kikusui
  • Organizer: 日本神経科学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-27
  • Invited
• [Presentation] Early weaning impaired fear extinction and decreased BDNF expression in the prefrontal cortex in adult C57BL/6 mice (2015)
  • Author(s): Kazutaka Mogi and Takefumi Kikusui
  • Organizer: 日本神経科学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-27
• [Presentation] Individual differences in mice courtship vocalizations are correlated with sexual emotion and neuronal activity in the ventral tegmental area (2015)
  • Author(s): Kouta Kanno and Takefumi Kikusui
  • Organizer: 日本神経科学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-07-27
• [Remarks] 伴侶動物研究室Publication
  • URL: https://sites.google.com/a/carazabu.com/car/publications
• [Remarks] 麻布大学獣医学部伴侶動物学研究室
  • URL: https://sites.google.com/a/carazabu.com/car/