Unveiling vulnerability of the neural connectivity controlling nicotine intake in marmoset brain development

• Project/Area Number: 19K16031
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: Seki Fumiko 公益財団法人実験動物中央研究所, ライブイメージングセンター, 主任 (40771407)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: マーモセット / MRI / 脳活動 / 発達 / 手綱核 / functional / 可塑性 / fMRI / ニコチン / 脳発達 / 中毒

Outline of Research at the Start

子どもは喫煙開始後すぐニコチン依存に陥り易いが、その脆弱性の基礎にある子どもの脳神経基盤は不明である。
回路が抑制時の認知行動と脳活動は脳の発達度合いによって変化するかを明らかにするために、ヒトと脳発達パターンがより類似している非ヒト霊長類のコモンマーモセットを適用する。同一個体が子どもから大人へ変化し脳成熟することに依って、ニコチン手綱核-脚間核回路の抑制時に見られた症状は変化するかを明らかにする。

Outline of Final Research Achievements

The project aimed to establish the method for evaluating brain activity associated with habenular nucleus - interpeduncular nucleus connection using MRI and cognitive assessment. If neural activity of habenular - interpeduncular nucleus connectivity is restrained by use of chemogenetic technology, its activity would be similar to the neural activity when we take nicotine.
The high resolution and high contrast MRI were acquired to visualize the connectivity between habenular nucleus and interpeduncular nucleus. Also, functional MRI was optimized to evaluate the activation at the whole brain level. In addition, longitudinal MRI was conducted to identify when the volume change due to development lasted. It was found that the volume decrease was continued after the age of 24 months, the timepoint of adulthood. Such base data would contribute to evaluate the brain activity changed associated with brain development or intervention.

Academic Significance and Societal Importance of the Research Achievements

非ヒト霊長類である実験動物のマーモセットは、他霊長類と比べ発達期間が短くヒトの脳発達を理解する上で適したモデルの一つである。マーモセットとヒトと共通したMRIをモダリティとして使用出来ればスムースな比較研究が可能となる。本研究ではマーモセットの脳発達を多面的に評価するための基盤を確立した。マーモセットの発達に伴う脳形態の変化はヒトと同様性成熟に達する年齢より長く変化することを見出した。また覚醒下における全脳活動を評価する方法を確立した。これらから子どもがより脆弱とされているニコチン依存について、脳発達の度合いがもたらす影響について評価するデータを整えた。

Research Products

• [Journal Article] The common marmoset in biomedical research: experimental disease models and veterinary management (2023)
  • Author(s): INOUE Takashi、YURIMOTO Terumi、SEKI Fumiko、SATO Kenya、SASAKI Erika
  • Journal Title: Experimental Animals Volume: 72 Issue: 2 Pages: 140-150
  • DOI: 10.1538/expanim.22-0107
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access
• [Journal Article] Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter. (2022)
  • Author(s): Yoshimatsu S, Seki F, Okahara J, Watanabe H, Sasaguri H, Haga Y, Hata JI, Sanosaka T, Inoue T, Mineshige T, Lee CY, Shinohara H, Kurotaki Y, Komaki Y, Kishi N, Murayama AY, Nagai Y, Minamimoto T, Yamamoto M, Nakajima M, Zhou Z, Nemoto A, Sato T, Ikeuchi T, Sahara N, Morimoto S, Shiozawa S, Saido TC, Sasaki E, Okano H
  • Journal Title: Neuroscience Research Volume: 185 Pages: 49-61
  • DOI: 10.1016/j.neures.2022.08.008
  • Peer Reviewed / Open Access
• [Journal Article] Effect of sedatives or anesthetics on the measurement of resting brain function in common marmosets (2022)
  • Author(s): Muta Kanako、Hata Junichi、Kawaguchi Naoki、Haga Yawara、Yoshimaru Daisuke、Hagiya Kei、Kaneko Takaaki、Miyabe-Nishiwaki Takako、Komaki Yuji、Seki Fumiko、Okano Hirotaka James、Okano Hideyuki
  • Journal Title: Cerebral Cortex Volume: 33 Issue: 9 Pages: 5148-5162
  • DOI: 10.1093/cercor/bhac406
  • Peer Reviewed / Open Access
• [Journal Article] Effects of chronic caffeine intake and withdrawal on neural activity assessed via resting-state functional magnetic resonance imaging in mice (2022)
  • Author(s): Rikitake Mitsuki、Notake Sachiko、Kurokawa Karen、Hata Junichi、Seki Fumiko、Komaki Yuji、Oshiro Hinako、Kawaguchi Naoki、Haga Yawara、Yoshimaru Daisuke、Ito Ken、Okano Hirotaka James
  • Journal Title: Heliyon Volume: 8 Issue: 11 Pages: e11714-e11714
  • DOI: 10.1016/j.heliyon.2022.e11714
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Volumetric Analysis of Mecp2-Null Mouse Model for Rett Syndrome by T2-Weighted 3D Magnetic Resonance Imaging (2022)
  • Author(s): Akaba Yuichi、Shiohama Tadashi、Komaki Yuji、Seki Fumiko、Ortug Alpen、Sawada Daisuke、Uchida Wataru、Kamagata Koji、Shimoji Keigo、Aoki Shigeki、Takahashi Satoru、Suzuki Takeshi、Natsume Jun、Takahashi Emi、Tsujimura Keita
  • Journal Title: Frontiers in Neuroscience Volume: 16 Pages: 1-13
  • DOI: 10.3389/fnins.2022.885335
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice (2021)
  • Author(s): Abe Yoshifumi、Kwon Soojin、Oishi Mitsuhiro、Unekawa Miyuki、Takata Norio、Seki Fumiko、Koyama Ryuta、Abe Manabu、Sakimura Kenji、Masamoto Kazuto、Tomita Yutaka、Okano Hideyuki、Mushiake Hajime、Tanaka Kenji F.
  • Journal Title: Cell Reports Volume: 36 Issue: 4 Pages: 109427-109427
  • DOI: 10.1016/j.celrep.2021.109427
  • Peer Reviewed / Open Access
• [Journal Article] Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain (2020)
  • Author(s): Kawamura Atsuki、Abe Yoshifumi、Seki Fumiko、Katayama Yuta、Nishiyama Masaaki、Takata Norio、Tanaka Kenji F.、Okano Hideyuki、Nakayama Keiichi I.
  • Journal Title: Molecular Brain Volume: 13 Issue: 1 Pages: 160-160
  • DOI: 10.1186/s13041-020-00699-x
  • Peer Reviewed / Open Access
• [Journal Article] MR Imaging Properties of <i>ex vivo</i> Common Marmoset Brain after Formaldehyde Fixation (2019)
  • Author(s): Haga Yawara、Hata Junichi、Uematsu Akiko、Seki Fumiko、Komaki Yuji、Mizumura Mai、Nishio Marin、Kaneko Takaaki、Kishi Noriyuki、Okano Hideyuki、Furukawa Akira
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 18 Issue: 4 Pages: 253-259
  • DOI: 10.2463/mrms.mp.2018-0086
  • NAID: 130007728812
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed / Open Access
• [Presentation] 豊かな環境で育ったマーモセットの脳発達解析 (2023)
  • Author(s): 2.関 布美子、冨樫 充良、村岡 俊典、黒滝 陽子、井上 貴史、圦本 晃海、向笠 圭亮、小牧 裕司、山田 知歩子、佐々木 えりか
  • Organizer: マーモセット研究会
• [Presentation] 環境エンリッチメントが脳発達に与える影響 (2022)
  • Author(s): 1.関 布美子、冨樫 充良、村岡 俊典、石淵 智子、黒滝 陽子、井上 貴史、圦本 晃海、向笠 圭亮、小牧 裕司、山田 知歩子、力武 聖月、伊東 莉那、佐々木 えりか
  • Organizer: 日本神経科学学会
• [Presentation] 環境エンリッチメントが脳発達に与える影響 (2022)
  • Author(s): 1.関布美子、山田知歩子、小牧裕司、冨樫充良、村岡俊典、石淵智子、黒滝陽子、井上貴史、圦本晃海、向笠圭亮、力武聖月、伊東莉那、佐々木えりか
  • Organizer: 第11回マーモセット研究会
• [Presentation] Functional MRI in awake marmosets for longitudinal studies. (2021)
  • Author(s): F. Seki, T. Yurimoto, T. Inoue, E. Sasaki.
  • Organizer: Neuroscience 2021 Annual meeting of Society for Neuroscience
  • Int'l Joint Research
• [Presentation] Longitudinal voxel-based analysis in Alzheimer’s disease transgenic marmosets (2020)
  • Author(s): Fumiko Seki Seiji Shiozawa Sho Yoshimatsu Yuji Komaki Marin Nishio Erika Sasaki Hideyuki Okano
  • Organizer: International Society for Magnetic Resonance in Medicine
  • Int'l Joint Research
• [Presentation] MR Neuroimaging of disease models in the common marmoset (2019)
  • Author(s): Fumiko Seki
  • Organizer: 2019 International Symposium of Korean Association for Laboratory Animal Sciences
  • Int'l Joint Research / Invited
• [Presentation] Multiparametric analysis of life-span brain maturation and degeneration in common marmosets brain (2019)
  • Author(s): Fumiko Seki
  • Organizer: 日本神経科学会
• [Presentation] Evaluation of cortical microstructure in marmoset life-span development (2019)
  • Author(s): Fumiko Seki
  • Organizer: 日本マーモセット研究会
• [Patent(Industrial Property Rights)] 機能的ＭＲＩ用ベッド及びこれを備えた 機能的ＭＲＩ用ベッドシステム (2021)
  • Inventor(s): 2021
  • Industrial Property Rights Holder: 2021
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2021-110184
  • Filing Date: 2021