Function of sexually dimorphic cell groups for sexually dimorphic behavior

• Project/Area Number: 21K06414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Toho University
• Principal Investigator: Tsuneoka Yousuke 東邦大学, 医学部, 准教授 (50549011)
• Co-Investigator(Kenkyū-buntansha): 船戸 弘正 東邦大学, 医学部, 教授 (90363118)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 性的二型 / 内側視索前野 / 性行動 / 本能行動 / 神経回路 / Penk / 多重蛍光ISH / Creマウス / DREADD / AAV

Outline of Research at the Start

哺乳類の中枢神経系に広くみられる性的二型は性特異的もしくは性差のある行動の制御に関わっていると考えられているが、一部の例を除いて、脳の構造的性差が行動に与える影響は不明であった。申請者らは内側視索前野・分界条床核・扁桃体における3か所に性的二型核が存在し、2種の細胞が3領域で共通して分布することを発見した。、この性的二型細胞集団が行動の性差の責任領域の一つなのかについて検討するため、その解剖学的特徴づけを行うと共に、その機能を解明することを目的とする。

Outline of Final Research Achievements

To verify the function of sexually dimorphic cell groups in the medial preoptic area of hypothalamus, we analyzed the anatomy of those cells, as well as their function by manipulating neural activity using genetically engineered mice and adeno-associated virus. Even within the sexually dimorphic group of cells, sex steroid hormones' sensitivity differed among cell types. We developed a multiple ISH method to histologically clarify the timing of activity of these cells. Based on this information, we performed manipulation experiments and identified a group of neurons involved in the motivational regulation of sexual behavior.

Academic Significance and Societal Importance of the Research Achievements

これまで、性的二型核はその存在は知られていたものの、どのような種類の細胞なのかは明らかになっていなかった。また、どれだけの種類の細胞があるのかについても不明であった。本研究では内側視索前野の性的二型核に存在する細胞群として3種類の細胞を同定するとともに、その機能の一端を明らかにした。また、その過程で新規のイメージング技術の開発にも成功した。

Research Products

• [Journal Article] Subcellular localization of Na+/K+-ATPase isoforms resolved by in situ hybridization chain reaction in the gill of chum salmon at freshwater and seawater (2023)
  • Author(s): Wong Marty Kwok Shing、Tsuneoka Yousuke、Tsukada Takehiro
  • Journal Title: Fish Physiology and Biochemistry Volume: 49 Issue: 4 Pages: 751-767
  • DOI: 10.1007/s10695-023-01212-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of TRPM8-expressing neurons in the adult mouse hypothalamus (2023)
  • Author(s): Tsuneoka Yousuke、Nishikawa Taichi、Furube Eriko、Okamoto Kaho、Yoshimura Ryoichi、Funato Hiromasa、Miyata Seiji
  • Journal Title: Neuroscience Letters Volume: 814 Pages: 137463-137463
  • DOI: 10.1016/j.neulet.2023.137463
  • Peer Reviewed
• [Journal Article] Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior. (2023)
  • Author(s): M Morishita, K Kobayashi, M Mitsuzuka, R Takagi, K Ono, R Momma, Y Tsuneoka, S Horio, S Tsukahara
  • Journal Title: J Neurosci Volume: 43 Issue: 44 Pages: 7322-7336
  • DOI: 10.1523/jneurosci.0361-23.2023
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin Facilitates Allomaternal Behavior under Stress in Laboratory Mice (2022)
  • Author(s): Tsuneoka Yousuke、Yoshihara Chihiro、Ohnishi Ryuko、Yoshida Sachine、Miyazawa Eri、Yamada Masanobu、Horiguchi Kazuhiko、Young W. Scott、Nishimori Katsuhiko、Kato Tadafumi、Kuroda Kumi O.
  • Journal Title: eneuro Volume: 9(1): ENEURO.0405-21.2022 Issue: 1 Pages: 1-22
  • DOI: 10.1523/eneuro.0405-21.2022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene duplication of C-type natriuretic peptide-4 (CNP4) in teleost lineage elicits subfunctionalization of ancestral CNP (2022)
  • Author(s): Katayama Yukitoshi、Saito Ami、Ogoshi Maho、Tsuneoka Yousuke、Mukuda Takao、Azuma Morio、Kusakabe Makoto、Takei Yoshio、Tsukada Takehiro
  • Journal Title: Cell and Tissue Research Volume: 388 Issue: 2 Pages: 225-238
  • DOI: 10.1007/s00441-022-03596-y
  • Peer Reviewed
• [Journal Article] IκBζ controls IL-17-triggered gene expression program in intestinal epithelial cells that restricts colonization of SFB and prevents Th17-associated pathologies (2022)
  • Author(s): Yamazaki Soh、Inohara Naohiro、Ohmuraya Masaki、Tsuneoka Yousuke、Yagita Hideo、Katagiri Takaharu、Nishina Takashi、Mikami Tetuo、Funato Hiromasa、Araki Kimi、Nakano Hiroyasu
  • Journal Title: Mucosal Immunology Volume: 15 Issue: 6 Pages: 1321-1337
  • DOI: 10.1038/s41385-022-00554-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluorescence quenching by high-power LEDs for highly sensitive fluorescence in situ hybridization (2022)
  • Author(s): Tsuneoka Yousuke、Atsumi Yusuke、Makanae Aki、Yashiro Mitsuru、Funato Hiromasa
  • Journal Title: Frontiers in Molecular Neuroscience Volume: 15 Pages: 976349-976349
  • DOI: 10.3389/fnmol.2022.976349
  • Peer Reviewed / Open Access
• [Journal Article] Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care (2021)
  • Author(s): Yoshihara, C., Tokita, K., Maruyama, T., Kaneko, M., Tsuneoka, Y., Fukumitsu, K., Miyazawa, E., Shinozuka, K., Huang, A.J., Nishimori, K., McHugh, T.J., Tanaka, M., Itohara, S., Touhara, K., Miyamichi, K., Kuroda, K.O.
  • Journal Title: Cell Reports Volume: 35(9) Issue: 9 Pages: 109204-109204
  • DOI: 10.1016/j.celrep.2021.109204
  • Peer Reviewed / Open Access
• [Presentation] ISHpaletteの原理とその応用 (2023)
  • Author(s): 恒岡洋右
  • Organizer: 第56回発生学会
  • Invited
• [Presentation] Penk neurons in the central part of the medial preoptic area regulate sexual arousal. (2023)
  • Author(s): Tsuneoka Y, Kanno K, Funato H
  • Organizer: 第46回神経科学学会
• [Presentation] 短鎖ヘアピンDNAを用いた改良in situ hybridization chain reaction法の開発 (2023)
  • Author(s): 恒岡洋右
  • Organizer: 第94回日本動物学会
  • Invited
• [Presentation] 短鎖ヘアピンDNAを用いた高感度 in situ hybridization法の原理と応用 (2023)
  • Author(s): 恒岡洋右
  • Organizer: 第49回神経内分泌学会
  • Invited
• [Presentation] Branched HCR法によって明らかになったマウス脳内オレキシン受容体mRNAの分布 (2023)
  • Author(s): 恒岡洋右, 船戸弘正
  • Organizer: 日本解剖学会128回大会
• [Presentation] 高感度超多重ISH法から観る内側視索前野のオス性行動における機能 (2022)
  • Author(s): 恒岡洋右, 船戸弘正
  • Organizer: 第48回神経内分泌学会
• [Presentation] 性と経験によって変化するマウス養育行動 (2022)
  • Author(s): 恒岡洋右
  • Organizer: 第93回日本動物学会
  • Invited
• [Patent(Industrial Property Rights)] 自家蛍光消光装置 (2021)
  • Inventor(s): 恒岡洋右、船戸弘正
  • Industrial Property Rights Holder: 恒岡洋右、船戸弘正、(株)ネッパジーン
  • Industrial Property Rights Type: 特許
  • Filing Date: 2021
  • Overseas