The study for the developmental mechanism of sociality which is specific to mammalian species

• Project/Area Number: 18H02356
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Azabu University
• Principal Investigator: Mogi Kazutaka 麻布大学, 獣医学部, 教授 (50347308)
• Co-Investigator(Kenkyū-buntansha): 守口 徹 麻布大学, 生命・環境科学部, 教授 (10512006) ; 宮内 栄治 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員(移行) (60634706)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: 社会適応性 / オキシトシン / 発達 / 人工哺乳 / 細菌叢 / 母子関係 / 帯状回皮質 / 社会行動 / 社会記憶

Outline of Final Research Achievements

The purpose of this study was to elucidate the mechanism by which "social adaptability" in mammalian animals develops by maternal factors. First, we found that the infant-specific oxytocin nervous system is one of the neural systems responsible for the development of social adaptability. We also searched for a new responsible nervous system and found that there are memory cells in the paraventricular nucleus of thalamus and hippocampal dentate gyrus that are activated both by maternal stimuli in infancy and during maternal behavior in adulthood. We focused on maternal licking/grooming as one of the maternal factors, and found that pain sensitivity increased when caress-sensitive nerves in the pups were specifically suppressed in the early stages of life. From experiments using artificially reared mice, we also found that Lactobacillus in mother's milk is a maternal factor that promotes the development of sociability and cognitive ability in the pups.

Academic Significance and Societal Importance of the Research Achievements

動物がその繁殖能力や環境への適応能力を最大限発揮するためには、他個体を適切に認知し、社会的状況に適した行動や社会的ストレスを軽減させるような生理反応を引き起こす“社会適応性”が必須である。本研究は、社会適応性が母からの適切な母性因子により発達することを明らかにし、その神経学的メカニズムを初めて明らかにした。また、社会適応性発達に関わる母性因子として、母からの撫で刺激の重要性を実証するとともに、母乳中の乳酸菌も母性因子の一つであることを示した。これらの知見は今後の適切な動物飼育方法に加え、人の育児スタイルの在り方にも影響を与える。また社会適応性発達を考慮した人工乳開発などへの応用も考えられる。

Research Products

• [Int'l Joint Research] New York University/School of Medicine(米国)
• [Int'l Joint Research] New York University/School of Medicine(米国)
• [Int'l Joint Research] NYU School of Medicine(米国)
• [Journal Article] Influence of ω3 fatty acids on maternal behavior and brain oxytocin in the murine perinatal period. (2022)
  • Author(s): A. Harauma, S. Nakamura, N. Wakinaka, K. Mogi, T. Moriguchi
  • Journal Title: Prostaglandins, Leukotrienes and Essential Fatty Acids Volume: 176 Pages: 102386-102386
  • DOI: 10.1016/j.plefa.2021.102386
  • Peer Reviewed
• [Journal Article] The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology. (2022)
  • Author(s): R. Buffenstein, V. Amorosa, B. Andziak, S. Avdieiev, J. Azpurua, ......, K. Mogi, et al.
  • Journal Title: Biological Reviews Volume: 97(1) Issue: 1 Pages: 115-140
  • DOI: 10.1111/brv.12791
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Testosterone Increases the Emission of Ultrasonic Vocalizations With Different Acoustic Characteristics in Mice (2021)
  • Author(s): Kikusui Takefumi、Sonobe Miku、Yoshida Yuuki、Nagasawa Miho、Ey Elodie、de Chaumont Fabrice、Bourgeron Thomas、Nomoto Kensaku、Mogi Kazutaka
  • Journal Title: Frontiers in Psychology Volume: 12 Pages: 680176-680176
  • DOI: 10.3389/fpsyg.2021.680176
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oxytocin neurons enable social transmission of maternal behaviour (2021)
  • Author(s): Carcea I、Caraballo N、Marlin B、Ooyama R、Riceberg J、Mendoza N、Opendak M、Diaz V、Schuster L、Alvarado T、Lethin H、Ramos D、Minder J、Mendoza S、Bair-Marshall C、Samadjopoulos G、Hidema S、Falkner A、Lin D、Mar A、Wadghiri Y、Nishimori K、Kikusui T、Mogi K、Sullivan R、Froemke R.
  • Journal Title: Nature Volume: 596 Issue: 7873 Pages: 553-557
  • DOI: 10.1038/s41586-021-03814-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Basal cortisol concentrations related to maternal behavior during puppy development predict post-growth resilience in dogs. (2021)
  • Author(s): M. Nagasawa, Y. Shibata, A. Yonezawa, T. Takahashi, M. Kanai, H. Ohtsuka, Y. Suenaga, Y. Yabana, K. Mogi, T. Kikusui.
  • Journal Title: Hormones and Behavior Volume: 136 Pages: 105055-105055
  • DOI: 10.1016/j.yhbeh.2021.105055
  • Peer Reviewed
• [Journal Article] Low maternal licking/grooming stimulation increases pain sensitivity in male mouse offspring. (2021)
  • Author(s): T. Sakamoto, Y Ishio, Y Ishida, K. Mogi, T. Kikusui
  • Journal Title: Experimental Animals Volume: 70(1) Issue: 1 Pages: 13-21
  • DOI: 10.1538/expanim.20-0030
  • NAID: 130007981761
  • Peer Reviewed / Open Access
• [Journal Article] The olfactory critical period is determined by activity-dependent Sema7A/PlxnC1 signaling within glomeruli (2021)
  • Author(s): Inoue N, Nishizumi H, Ooyama R, Mogi K, Nishimori K, Kikusui T, Sakano H
  • Journal Title: eLife Volume: 10 Pages: 65078-65078
  • DOI: 10.7554/elife.65078
  • Peer Reviewed / Open Access
• [Journal Article] Testosterone regulates the emission of ultrasonic vocalizations and mounting behavior during different developmental periods in mice (2020)
  • Author(s): Kikusui Takefumi、Shima Yuichi、Sonobe Miku、Yoshida Yuuki、Nagasawa Miho、Nomoto Kensaku、Mogi Kazutaka
  • Journal Title: Developmental Psychobiology Volume: 0 Issue: 4 Pages: 0-0
  • DOI: 10.1002/dev.22045
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maternal approach behaviors toward neonatal calls are impaired by mother's experiences of raising pups with a risk gene variant for autism. (2020)
  • Author(s): Risa Kato, Akihiro Machida, Kensaku Nomoto, Gina Kang, Takeshi Hiramoto, Kenji Tanigaki, Kazutaka Mogi, Noboru Hiroi, Takefumi Kikusui
  • Journal Title: Dev Psychobiol Volume: 63 Issue: 1 Pages: 108-113
  • DOI: 10.1002/dev.22006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The blockade of oxytocin receptors in the paraventricular thalamus reduces maternal crouching behavior over pups in lactating mice. (2020)
  • Author(s): A. Watarai, S. Tsutaki, K. Nishimori, T. Okuyama, K. Mogi, T. Kikusui
  • Journal Title: Neuroscience Letters Volume: 720 Pages: 134761-134761
  • DOI: 10.1016/j.neulet.2020.134761
  • Peer Reviewed
• [Journal Article] Gonadal steroid hormone secretion during the juvenile period depends on host-specific microbiota and contributes to the development of odor preference (2019)
  • Author(s): Kamimura Itsuka、Watarai Akiyuki、Takamura Takuma、Takeo Atsushi、Miura Kyoko、Morita Hidetoshi、Mogi Kazutaka、Kikusui Takefumi
  • Journal Title: Developmental Psychobiology Volume: in press Issue: 5 Pages: 670-678
  • DOI: 10.1002/dev.21827
  • Peer Reviewed / Open Access
• [Journal Article] Low maternal care enhances the skin barrier resistance of offspring in mice (2019)
  • Author(s): Sakamoto Takashi、Ishio Yukino、Ishida Yuiko、Mogi Kazutaka、Kikusui Takefumi
  • Journal Title: PLOS ONE Volume: 14 Issue: 7 Pages: e0219674-e0219674
  • DOI: 10.1371/journal.pone.0219674
  • Peer Reviewed / Open Access
• [Journal Article] Early weaning increases anxiety via brain-derived neurotrophic factor signaling in the mouse prefrontal cortex (2019)
  • Author(s): Kikusui Takefumi、Kanbara Natsumi、Ozaki Mariya、Hirayama Nozomi、Ida Kumiko、Tokita Mika、Tanabe Naho、Mitsuyama Kuriko、Abe Hatsuki、Yoshida Miki、Nagasawa Miho、Mogi Kazutaka
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 3991-3991
  • DOI: 10.1038/s41598-019-40530-9
  • Peer Reviewed / Open Access
• [Journal Article] Sex differences in olfactory-induced neural activation of the amygdala. (2018)
  • Author(s): Kikusui T, Kajita M, Otsuka N, Hattori T, Kumazawa K, Watarai A, Nagasawa M, Inutsuka A, Yamanaka A, Matsuo N, Covington HE 3rd, Mogi K.
  • Journal Title: Behav Brain Res. Volume: 27 Pages: 96-104
  • DOI: 10.1016/j.bbr.2017.11.034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of the Oxytocin Receptor Gene Polymorphism on Successful Training for Drug Detection Dogs. (2018)
  • Author(s): Konno A, Yabuta S, Inoue-Murayama M, Tonoike A, Nagasawa M, Mogi K, Kikusui T
  • Journal Title: Journal of Heredity Volume: - Issue: 5 Pages: 0-0
  • DOI: 10.1093/jhered/esy012
  • Peer Reviewed
• [Journal Article] Responses to pup vocalizations in subordinate naked mole-rats are induced by estradiol ingested through coprophagy of queen’s feces (2018)
  • Author(s): Watarai Akiyuki、Arai Natsuki、Miyawaki Shingo、Okano Hideyuki、Miura Kyoko、Mogi Kazutaka、Kikusui Takefumi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 37 Pages: 9264-9269
  • DOI: 10.1073/pnas.1720530115
  • Peer Reviewed / Open Access
• [Journal Article] Female mice exhibit both sexual and social partner preferences for vocalizing males (2018)
  • Author(s): NOMOTO Kensaku、IKUMI Mayu、OTSUKA Monami、ASABA Akari、KATO Masahiro、KOSHIDA Nobuyoshi、MOGI Kazutaka、KIKUSUI Takefumi
  • Journal Title: Integrative Zoology Volume: 13 Issue: 6 Pages: 735-744
  • DOI: 10.1111/1749-4877.12357
  • Peer Reviewed / Open Access
• [Presentation] 出生時期の母からの細菌叢伝播が子マウスの行動発達に及ぼす影響 (2021)
  • Author(s): 三國史佳、宮内栄治、久世明香、菊水健史、茂木一孝
  • Organizer: 第164回日本獣医学会学術集会
• [Presentation] 母性行動形質の次世代伝承への腸内細菌叢の関与のノトバイオートマウスを用いた検討 (2021)
  • Author(s): 秋山潤、水田真未、山岡未来、上村いつか、久世明香、茂木一孝、菊水健史
  • Organizer: 第164回日本獣医学会学術集会
• [Presentation] アルツハイマー型認知症腸内細菌叢ノトバイオートマウスを用いた認知機能を低下させる細菌の探索 (2021)
  • Author(s): 水田真未、上村いつか 、 山岡未来 、秋山 潤 、茂木一孝 、菊水健史
  • Organizer: 第164回日本獣医学会学術集会
• [Presentation] イヌ飼育によるだ液細菌叢構成変化が宿主行動に影響を及ぼす (2021)
  • Author(s): 山岡未来、秋山潤、水田真未、上村いつか、安藤俊太郎、山崎修道、遠藤香織、 西田淳志、永澤美保、茂木一孝、菊水健史
  • Organizer: 第164回日本獣医学会学術集会
• [Presentation] Urinary mesotocin concentration and male-male affiliative relationships in large-billed crows (Corvus macrorhynchos) (2021)
  • Author(s): Akiko Seguchi、Kazutaka Mogi、Takefumi Kikusui、Ei-Ichi Izawa
  • Organizer: 動物心理学会第81回大会
• [Presentation] The effect of removal of the dominant individual on the fecal testosterone level of a group-housed crows (2021)
  • Author(s): Illia Aota、Mayu Takano、Yuki Mizuno、Chisato Yatsuda、Kazutaka Mogi、Takefumi Kikusui、Ei-Ichi Izawa
  • Organizer: 動物心理学会第81回大会
• [Presentation] Hierarchical fluctuations in a mice group by artificial neural manipulation of aggression (2021)
  • Author(s): Ryoko Shiraishi、Kensaku Nomoto、Kazutaka Mogi、Takefumi Kikusui
  • Organizer: 動物心理学会第81回大会
• [Presentation] Elucidation of the role of ACC in emotional transmission in mice (2021)
  • Author(s): Miki Sugihara、Kensaku Nomoto、Kazutaka Mogi、Takefumi Kikusui
  • Organizer: 動物心理学会第81回大会
• [Presentation] Localization of oxytocin receptors for observational fear (2021)
  • Author(s): Yumi Saito、Kazutaka Mogi、Takefumi Kikusui
  • Organizer: 動物心理学会第81回大会
• [Presentation] 早期離乳による行動発達変化への腸内細菌叢の関与 (2020)
  • Author(s): 茂木 一孝，上村 いつか，宮内 栄治，大野 博司，菊水 健史
  • Organizer: 第93回日本薬理学会年会 シンポジウム「疾病・心理ストレスによる組織恒常性の破綻と修復における多臓器連関」
• [Presentation] 前部帯状皮質は観察恐怖表出を制御する (2020)
  • Author(s): 野元 謙作、中村 月香、村山 花子、永井 一成、都田 真由子、林 佳佑、 杉原 樹、茂木 一孝、小出 剛、菊水 健史
  • Organizer: 第97回日本生理学会
• [Presentation] オキシトシンによる情動性の涙 (2019)
  • Author(s): 菊水 健史、村田 香織、今田 敏博、Kai Jin 、茂木 一孝、永澤 美保、中村 滋 、坪田 一男
  • Organizer: NEURO2019 Symposium: 情動的価値を制御する神経ペプチドの新しい役割
• [Presentation] Tbx1遺伝子ヘテロ欠損自閉症モデルマウスにおけるコミュニケーション能力の解析 (2019)
  • Author(s): 加藤 梨沙、町田 暁洋、野元 謙作、廣井 昇、茂木 一孝、菊水 健史
  • Organizer: NEURO2019
• [Presentation] 腸内細菌叢の組成変化は早期離乳ストレスによるうつ様行動に関連する (2019)
  • Author(s): 上村 いつか、宮内 栄治、土屋 範晃、田村 奏美、上杉 愛海、竹内 直志、茂木 一孝、大野 博司、菊水 健史
  • Organizer: NEURO2019
• [Presentation] 前部帯状皮質は観察恐怖表出を制御する (2019)
  • Author(s): 野元 謙作、中村 月香、村山 花子、永井 一成、都田 真由子、茂木 一孝、小出 剛、菊水 健史
  • Organizer: NEURO2019
• [Presentation] 早期離乳が成長後の社会行動発現に及ぼす影響 (2019)
  • Author(s): 柳 佑実、久世 明香、茂木 一孝、菊水 健史
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] マウスにおける母性行動形質の次世代伝承 (2019)
  • Author(s): 二川 夏実、田村 奏美、神谷 麻愛、久世 明香、茂木 一孝、菊水 健史
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] Oxytocin neurons enable social transmission of maternal behavior. (2019)
  • Author(s): I. C. Carcea, N. Lopez, B. J. Marlin, R. Oyama, J. Mendoza-Navarpo, M. Opendak, A. L. Falkner, D. Lin, K. Nishimori, T. Kikusui, K. Mogi, R. M. Sullivan, R. C. Froemke
  • Organizer: NEUROSCIENCE 2019
  • Int'l Joint Research
• [Presentation] Oxytocin modurates emotional tears. (2019)
  • Author(s): T. Kikusui, K. Murata, T. Imada, K. Jin, N. Kanemaki, K. Nishimori, K. Mogi, M. Nagasawa, S. Nalamura, K. Tsubota
  • Organizer: The Third Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Social communicative ability in a mouse autism model. (2019)
  • Author(s): R. Kato, A. Machida, K. Nomoto, N. Hiroi, K. Mogi, T. KIkusui
  • Organizer: The Third Sino-Japan Symposium on the Frontier of Behavioral Neuroendocrinology
  • Int'l Joint Research
• [Presentation] Social Transmission of Maternal Behavior (2018)
  • Author(s): Ioana Carcea, Rumi Oyama, Joyce Mendoza, Daniel Ramos, Naomi Lopez, Kazutaga Mogi, Takefumi Kikusui, Regina Sullivan, Robert Froemke
  • Organizer: The 41st Annual Meeting of the Japan Neuroscience Society
• [Presentation] Inhibition of corticosterone synthesis with metyrapone reduces pro-social behavior in rats (2018)
  • Author(s): Madoka Nakamura, Yuri Sugano, Kazutaka Mogi, Peggy Mason, Takefumi Kikusui
  • Organizer: The 78th Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] Social communicative ability in a mouse autism model (2018)
  • Author(s): Risa Kato, Akihiro Machida, Kensaku Nomoto, Noboru Hiroi, Kazutaka Mogi, Takefumi Kikusui
  • Organizer: The 78th Annual Meeting of the Japanese Society for Animal Psychology
• [Presentation] 早期離乳マウス由来の糞便細菌叢はストレス応答性の発達に影響を与える (2018)
  • Author(s): 上村いつか、土屋 範晃、田村 奏美、上杉 愛海、竹内 直志、宮内 栄治、茂木 一孝、大野 博司、菊水 健史
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] マウスの内側前頭前皮質（mPFC）から視床室傍核（PVT）への投射は母性行動を低下させる (2018)
  • Author(s): 目黒拓也、度会晃行、犬束歩、茂木一孝、菊水健史
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] 長期的・短期的な母乳授乳経験とオキシトシンホルモンが母親の情動知覚処理に与える影響 (2018)
  • Author(s): 松永倫子、菊水健史、茂木一孝、永澤美保、大山瑠泉、明和政子
  • Organizer: 日本心理学会第82回大会
• [Presentation] マウスの発達研究からみる触覚コミュニケーションの役割 (2018)
  • Author(s): 茂木一孝
  • Organizer: 日本発達心理学会第30回大会
  • Invited