マウス体性感覚野をモデルとした大脳皮質回路の早期スクラップ＆ビルドの解析

• Project Area: Dynamic regulation of brain function by Scrap & Build system
• Project/Area Number: 16H06459
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institute of Genetics
• Principal Investigator: 岩里 琢治 国立遺伝学研究所, 遺伝形質研究系, 教授 (00311332)
• Co-Investigator(Kenkyū-buntansha): 下郡 智美 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (30391981)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Project Status: Granted (Fiscal Year 2020)
• Budget Amount: ¥158,990,000 (Direct Cost: ¥122,300,000、Indirect Cost: ¥36,690,000); Fiscal Year 2020: ¥31,200,000 (Direct Cost: ¥24,000,000、Indirect Cost: ¥7,200,000); Fiscal Year 2019: ¥30,550,000 (Direct Cost: ¥23,500,000、Indirect Cost: ¥7,050,000); Fiscal Year 2018: ¥30,030,000 (Direct Cost: ¥23,100,000、Indirect Cost: ¥6,930,000); Fiscal Year 2017: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000); Fiscal Year 2016: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
• Keywords: 神経科学 / 神経回路 / 大脳皮質 / 発達 / 哺乳類 / 神経活動 / 神経回路発達 / 体性感覚野 / 樹状突起 / マウス / イメージング / 脳 / 遺伝学 / 回路形成

Outline of Annual Research Achievements

哺乳類の大脳皮質の神経回路が正常に発達するためには、生後発達の初期に自発活動や感覚入力などの神経活動によるスクラップアンドビルドを受けることが必要である。我々はマウス体性感覚野をモデルとしてそのメカニズムの解明を目指している。バレル形成中にあたる生後5日目のマウスの大脳皮質体性感覚野にパッチワーク型の自発活動が観察され、それが視床皮質軸索を介して末梢から大脳皮質第4層へと伝達されることを先に報告した。本年度はより詳細な解析を行い、バレル形成前にあたる生後1日目の段階ですでにパッチワーク型の活動が見られること、バレル形成が完了した生後9日目の段階ではパッチワーク型の活動はみられず、複数のバレルにまたがる広範な領域での同期活動が観察されることを明らかにした。そして、生後11日目には同じバレルに属する神経細胞であっても個別に活動し、体性感覚野全体でスパースに発火することを見つけた。このように生後2週間の間に体性感覚野第4層の自発活動の空間パターンは少なくとも３つのフェーズを遷移することが明らかとなった。また、これまでに大脳皮質体性感覚野の有棘星状細胞が神経活動依存的に樹状突起の形態変化を起こす分子メカニズムを明らかにしてきたが、これらの分子は脳室帯から生まれた興奮性神経細胞が有棘星状細胞に分化した時点で発現が起きる。一方で同じ脳室帯から生まれた錐体細胞にはこれらの分子が発現していないことから、錐体細胞と有棘星状細胞への分化が起きるタイミングでこれらの因子が発現するメカニズムを明らかにした。さらに、錐体細胞が有棘星状細胞に分化するための因子を同定していることから、この因子の発現を胎生期に操作することにより、体性感覚野に錐体細胞しか存在しないマウスの作製に成功した。このマウスの行動実験を行うと、ヒゲを使った物質の識別行動の一部に障害があることが明らかとなった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

生後発達期のマウス体性感覚野第4層にみられる自発活動に関して、前年度に発表した論文の研究を発展させる解析を進め、上述のとおり、様々な新しい知見が得られた。また、第4層神経細胞の分化の分子メカニズムに関しても、多くの知見が得られた。

Strategy for Future Research Activity

幼若期のマウス体性感覚野で観察される自発活動の空間パターンが発達段階とともに遷移するメカニズムを明らかにする。また、体性感覚野に有棘星状細胞がないマウスでは、神経回路が変化していることが考えられる。そこで、体性感覚野に錐体細胞しか存在しないマウスでの神経回路を狂犬病ウィルスなどを用いて明らかにし、有棘星状細胞の脳内での存在意義を明らかにする。

Research Products

• [Int'l Joint Research] UMH-CSIC(Spain)
• [Journal Article] NMDA Receptor Enhances Correlation of Spontaneous Activity in Neonatal Barrel Cortex (2020)
  • Author(s): Mizuno Hidenobu、Rao Madhura S.、Mizuno Hiromi、Sato Takuya、Nakazawa Shingo、Iwasato Takuji
  • Journal Title: The Journal of Neuroscience Volume: 41 Issue: 6 Pages: 1207-1217
  • DOI: 10.1523/jneurosci.0527-20.2020
  • Peer Reviewed
• [Journal Article] In vivo imaging of neural circuit formation in the neonatal mouse barrel cortex (2020)
  • Author(s): Iwasato Takuji
  • Journal Title: Development, Growth & Differentiation Volume: 62 Issue: 7-8 Pages: 476-486
  • DOI: 10.1111/dgd.12693
  • Peer Reviewed
• [Journal Article] Developmental Phase Transitions in Spatial Organization of Spontaneous Activity in Postnatal Barrel Cortex Layer 4 (2020)
  • Author(s): Nakazawa Shingo、Yoshimura Yumiko、Takagi Masahiro、Mizuno Hidenobu、Iwasato Takuji
  • Journal Title: The Journal of Neuroscience Volume: 40 Issue: 40 Pages: 7637-7650
  • DOI: 10.1523/jneurosci.1116-20.2020
  • Peer Reviewed / Open Access
• [Journal Article] Spatially restricted long‐term transgene expression in the developing skin used for studying the interaction of epidermal development and sensory innervation (2019)
  • Author(s): Chan Carmen、Kamiguchi Hiroyuki、Shimogori Tomomi
  • Journal Title: Development, Growth & Differentiation Volume: 00 Issue: 4 Pages: 1-7
  • DOI: 10.1111/dgd.12603
  • Peer Reviewed / Open Access
• [Journal Article] Genetically Encoded Fluorescent Indicator GRAPHIC Delineates Intercellular Connections (2019)
  • Author(s): Kinoshita Nagatoki、Huang Arthur J.Y.、McHugh Thomas J.、Suzuki Sachihiro C.、Masai Ichiro、Kim Il Hwan、Soderling Scott H.、Miyawaki Atsushi、Shimogori Tomomi
  • Journal Title: iScience Volume: 15 Pages: 28-38
  • DOI: 10.1016/j.isci.2019.04.013
  • Peer Reviewed / Open Access
• [Journal Article] Evolutionary Gain of Dbx1 Expression Drives Subplate Identity in the Cerebral Cortex (2019)
  • Author(s): Arai Yoko、Cwetsch Andrzej W.、Coppola Eva、Cipriani Sara、Nishihara Hidenori、Kanki Hiroaki、Saillour Yoann、Freret-Hodara Betty、Dutriaux Annie、Okada Norihiro、Okano Hideyuki、Dehay Colette、Nardelli Jeannette、Gressens Pierre、Shimogori Tomomi、D’Onofrio Giuseppe、Pierani Alessandra
  • Journal Title: Cell Reports Volume: 29 Issue: 3 Pages: 645-658.e5
  • DOI: 10.1016/j.celrep.2019.09.007
  • Peer Reviewed
• [Journal Article] In Vivo Two-photon Imaging of Cortical Neurons in Neonatal Mice (2018)
  • Author(s): Mizuno H*, Nakazawa S, Iwasato T (* correspondence)
  • Journal Title: Journal of Visualized Experiments Volume: 140 Issue: 140
  • DOI: 10.3791/58340
  • Peer Reviewed / Open Access
• [Journal Article] Differential dynamics of cortical neuron dendritic trees revealed by long-term in vivo imaging in neonates (2018)
  • Author(s): Nakazawa Shingo、Mizuno Hidenobu、Iwasato Takuji
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 3106-3106
  • DOI: 10.1038/s41467-018-05563-0
  • Peer Reviewed / Open Access
• [Journal Article] Development of tactile sensory circuits in the CNS (2018)
  • Author(s): Iwasato Takuji、Erzurumlu Reha S.
  • Journal Title: Current Opinion in Neurobiology Volume: 53 Pages: 66-75
  • DOI: 10.1016/j.conb.2018.06.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Patchwork-type spontaneous activity in neonatal barrel cortex layer 4 transmitted via thalamocortical projections. (2018)
  • Author(s): Mizuno, H., Ikezoe, K., Nakazawa, S., Sato, T., Kitamura, K., Iwasato, T.
  • Journal Title: Cell Rep. Volume: 22 Issue: 1 Pages: 123-135
  • DOI: 10.1016/j.celrep.2017.12.012
  • Peer Reviewed / Open Access
• [Journal Article] Protocadherin-αC2 is required for diffuse projections of serotonergic axons (2017)
  • Author(s): Katori Shota、Noguchi-Katori Yukiko、Okayama Atsushi、Kawamura Yoshimi、Luo Wenshu、Sakimura Kenji、Hirabayashi Takahiro、Iwasato Takuji、Yagi Takeshi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15908-15908
  • DOI: 10.1038/s41598-017-16120-y
  • Peer Reviewed / Open Access
• [Journal Article] Spinal RacGAP α-Chimaerin Is Required to Establish the Midline Barrier for Proper Corticospinal Axon Guidance (2017)
  • Author(s): Katori Shota、Noguchi-Katori Yukiko、Itohara Shigeyoshi、Iwasato Takuji
  • Journal Title: The Journal of Neuroscience Volume: 37 Issue: 32 Pages: 7682-7699
  • DOI: 10.1523/jneurosci.3123-16.2017
  • Peer Reviewed
• [Journal Article] Prenatal thalamic waves regulate cortical area size prior to sensory processing. (2017)
  • Author(s): Moreno-Juan, V., Filipchuk, A., Antoｎ-Bolarios, N., Mezzera, C., Gezelius, H., Andes, B., Rodriguez-Malmierca, L., Susin, R., Schaad, O., Iwasato, T., Schuele, R., Rutlin, M., Nelson, S., Ducret, S., Valdeolmillos, M., Rijli, F., Lopez-Bendito, G.
  • Journal Title: Nature Commun. Volume: 8 Issue: 1 Pages: 14172-14172
  • DOI: 10.1038/ncomms14172
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Supernova: A Versatile Vector System for Single-Cell Labeling and Gene Function Studies in vivo. (2016)
  • Author(s): Luo, W., Mizuno, H., Iwata, R., Nakazawa, S., Yasuda, K., Itohara, S., Iwasato, T.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 35747-35747
  • DOI: 10.1038/srep35747
  • Peer Reviewed / Open Access
• [Journal Article] In vitro Assay for Dendritic Spine Retraction of Hippocampal Neurons with Sparse Labeling. (2016)
  • Author(s): Iwata, R., Iwasato, T.
  • Journal Title: Bio-Protocol Volume: 6
  • Peer Reviewed / Open Access
• [Journal Article] CAPS1 stabilizes the state of readily releasable synaptic vesicles to fusion competence at CA3-CA1 synapses in adult hippocampus (2016)
  • Author(s): 6.Shinoda Y, Ishii C, Fukazawa Y, Sadakata T, Ishii Y, Sano Y, Iwasato T, Itohara S, Furuichi T
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 31540-31540
  • DOI: 10.1038/srep31540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 神経回路精緻化メカニズムの遺伝学的解析 (2021)
  • Author(s): 岩里琢治
  • Organizer: 新潟大学脳研究所共同利用共同研究合同セミナー
  • Invited
• [Presentation] マウス体性感覚野をモデルとした大脳皮質回路の早期スクラップ＆ビルドの解析 (Scrap and build of neural circuits in the neonatal mouse barrel cortex) (2020)
  • Author(s): 岩里琢治
  • Organizer: 第5回「スクラップ＆ビルド」領域会議
• [Presentation] マウス遺伝学を用いた体性感覚系神経回路発達の解析 (2020)
  • Author(s): 岩里琢治
  • Organizer: 2019年度脳研究所共同利用共同研究（笹岡班）合同セミナー
  • Invited
• [Presentation] マウス遺伝学を用いた体性感覚系神経回路発達の解析 (2020)
  • Author(s): 岩里琢治
  • Organizer: 2019年度脳研究所共同利用共同研究合同セミナー
  • Invited
• [Presentation] 新生仔期の大脳皮質における神経回路発達 (2019)
  • Author(s): 岩里琢治
  • Organizer: 認識と形成研究会2019
  • Invited
• [Presentation] Scrap and build of neural circuits in the neonatal mouse barrel cortex (2019)
  • Author(s): 岩里琢治
  • Organizer: 第4回「スクラップ＆ビルド」領域会議
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism. (2019)
  • Author(s): Tomomi Shimogori
  • Organizer: Keio University, Tokyo, Japan
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism. (2019)
  • Author(s): Tomomi Shimogori
  • Organizer: Kobe University, Kobe, Japan
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism. (2019)
  • Author(s): Tomomi Shimogori
  • Organizer: National Yang-Ming University, Taiwan
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism. (2019)
  • Author(s): Tomomi Shimogori
  • Organizer: National Cheng Kung University Taiwan
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism. (2019)
  • Author(s): Tomomi Shimogori
  • Organizer: IBRO-APRC School, Trivandrum, India
  • Int'l Joint Research / Invited
• [Presentation] 赤ん坊の脳の中での神経回路の発達 ―マウス遺伝学と二光子イメージングを用いた研究 (2019)
  • Author(s): 岩里琢治
  • Organizer: 第18回BIRD脳科学セミナー
  • Invited
• [Presentation] In vivo imaging of barrel cortex layer 4 during thalamocortical reorganization (2018)
  • Author(s): Takuji Iwasato
  • Organizer: 遺伝研研究会2018 “Circuit construction in the mammalian brain”
  • Invited
• [Presentation] In vivo imaging of barrel cortex circuit refinement in neonates (2018)
  • Author(s): Takuji Iwasato
  • Organizer: Spontaneous Activity in Brain Development (SPONT 2018)
  • Int'l Joint Research / Invited
• [Presentation] In vivo functional and morphological imaging of neural circuit refinement in the neonatal barrel cortex (2018)
  • Author(s): Takuji Iwasato
  • Organizer: CSHA(Cold Spring Harbor Asia) on Neuroscience 2018（コールドスプリングハーバー国際神経会議）「Latest Advances in Development and Function of Neuronal Circuits」サテライトシンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 新生仔マウスのバレル皮質神経回路発達のin vivoイメージング(In vivo imaging of barrel cortex circuit refinement in neonates) (2018)
  • Author(s): 岩里琢治
  • Organizer: 第41回日本神経科学大会
  • Invited
• [Presentation] マウスで迫る「赤ん坊の脳の発達のしくみ」 (2018)
  • Author(s): 岩里琢治
  • Organizer: JT生命誌研究館・国立遺伝学研究所共同企画シンポジウム「遺伝学の最先端研究から見る生命誌」
  • Invited
• [Presentation] Early life experience and brain development (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: Invited talk Zhejiang University
  • Invited
• [Presentation] Early life experience and brain development (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: Invited talk Capital Medical University
  • Invited
• [Presentation] Early life experience and brain development (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: The 5th Annual Meeting of Mongolian Neuroscience Society
  • Int'l Joint Research / Invited
• [Presentation] Thalamocortical input controls cell diversity in somatosernsory cortex (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: Gordon Research Conference (Molecular & Cellular Neurobiology)
  • Int'l Joint Research / Invited
• [Presentation] In vivo functional and morphological imaging of neural circuit refinement in the neonatal barrel cortex (2018)
  • Author(s): Takuji Iwasato
  • Organizer: CSHA(Cold Spring Harbor Asia) on Neuroscience 2018 「Latest Advances in Development and Function of Neuronal Circuits」サテライトシンポジウム
  • Int'l Joint Research / Invited
• [Presentation] Early life experience and brain development (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: UK-Japan Neuroscience Syposium, London, UK
  • Int'l Joint Research / Invited
• [Presentation] Input from the thalamus creates diversity of the cortical neuron (2018)
  • Author(s): Tomomi Shimogori
  • Organizer: Gordon Research Conference (Thalamocortical interactions), Il Ciocco, Italy
  • Int'l Joint Research / Invited
• [Presentation] マウス遺伝学を用いた体性感覚系神経回路発達の解析 (2017)
  • Author(s): 岩里琢治
  • Organizer: 新潟大学脳研究所共同研究合同セミナー
  • Invited
• [Presentation] Unveiling the mechanisms of neuronal circuit refinement in the neonatal mouse barrel Cortex (2017)
  • Author(s): Takuji Iwasato
  • Organizer: Academia Sinica Symposium
  • Int'l Joint Research / Invited
• [Presentation] マウス大脳皮質の生後発達期神経回路リモデリング (2017)
  • Author(s): 岩里琢治
  • Organizer: 第12回「認識と形成」研究会
  • Invited
• [Presentation] 生後発達期の大脳皮質リモデリング (2017)
  • Author(s): 岩里琢治
  • Organizer: 生理学研究所研究会「大脳皮質回路の機能原理を探る」
  • Invited
• [Presentation] マウス大脳皮質の生後発達期神経回路リモデリング (2017)
  • Author(s): 岩里琢治
  • Organizer: 第5回「幸福脳」研究会（名古屋大学・慶応大学合同ミーティング）
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: Indiana University, Linda and Jack Gill Chair of Neuroscience Department of Biology, Indiana, USA
  • Int'l Joint Research / Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: McGill University, Department of Physiology, Montreal, Canada
  • Int'l Joint Research / Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: The 48th NIPS symposium, Okazaki, Japan
  • Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: Boston Children’s Hospital, Harvard University, Boston, USA
  • Int'l Joint Research / Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: Depts of Cell Biology and Neurobiology, Duke university, North Carolina, USA
  • Int'l Joint Research / Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada
  • Int'l Joint Research / Invited
• [Presentation] Neuronal activity dependent circuit development: Morphological changes and molecular mechanism (2017)
  • Author(s): Tomomi Shimogori
  • Organizer: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
  • Int'l Joint Research / Invited
• [Presentation] Unveiling the mechanisms of neuronal circuit refinement in the neonatal mouse barrel Cortex (2017)
  • Author(s): 岩里琢治
  • Organizer: Academia Sinica Symposium
  • Int'l Joint Research / Invited
• [Presentation] 哺乳類中枢神経系における神経回路形成の遺伝学的解析 (2017)
  • Author(s): 岩里琢治
  • Organizer: 新潟大学脳研究所共同研究合同セミナー
  • Invited
• [Presentation] In vivo imaging of neonatal mouse barrel cortex (2016)
  • Author(s): T. Iwasato
  • Organizer: Dart Neuroscience Seminar Series at The Scripps Research Institute
  • Int'l Joint Research / Invited
• [Presentation] 新生仔大脳皮質における神経回路スクラップ&ビルド (2016)
  • Author(s): 岩里琢治
  • Organizer: スクラップ&ビルドによる脳機能の動的制御シンポジウム
  • Invited
• [Presentation] 独自の二光子イメージング技術を用いた、新生仔マウス大脳皮質における神経回路発達の解析 (2016)
  • Author(s): 岩里琢治
  • Organizer: 第159回日本獣医学会学術集会
  • Invited
• [Presentation] In vivo imaging of neonatal mouse barrel cortex (2016)
  • Author(s): T. Iwasato
  • Organizer: シンポジウム”Circuit Construction in the Mammalian Brain”
  • Int'l Joint Research / Invited
• [Patent(Industrial Property Rights)] ベクターシステム、遺伝子発現方法、標的遺伝子ノックアウト方法、標的遺伝子ノックダウン方法、標的遺伝子編集方法、及び遺伝子発現キット (2016)
  • Inventor(s): 岩里琢治、水野秀信、羅ブンジュウ、岩田亮平
  • Industrial Property Rights Holder: 情報・システム研究機構
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016
  • Acquisition Date: 2021