Anatomical and functional mapping in the cognitive behavior through the talamostriatal network

• Project/Area Number: 20K06912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Fukushima Medical University
• Principal Investigator: 加藤 成樹 福島県立医科大学, 医学部, 准教授 (90443879)
• Project Period (FY): 2020-04-01 – 2025-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 視床線条体 / 聴覚弁別行動 / 認知機能 / 大脳基底核

Outline of Research at the Start

視床を含む大脳基底核は、運動、認知、情動などの様々な脳機能を調節し、その異常は種々の精神・神経疾患の病態と深い関連を持つことが知られているが、神経回路レベルでの機能的な解析は進んでいない。本研究では、認知機能障害を伴うパーキンソン病において視床の神経細胞が一部変性することに着目し、視床線条体経路の認知機能における役割を解析することで、大脳基底核ネットワークの機能マッピングに取り組む。

Outline of Annual Research Achievements

自然界を生き抜く上で動物は生活環境におけるさまざまな情報を感覚系機能を通じて取得し、生命の危機を乗り越えている。その外界から受ける刺激の受容には大脳皮質のさまざまなsubregionと師匠の入出力関係、またそれを線条体がハブとして統御する重要な役割を担っている。解剖学的報告や近年のコネクトーム解析では、視床に含まれる束傍核(PF)と外側中心核(CL)から線条体へのグルタミン酸投射が、コリン作動性細胞を介して線条体の中型有棘神経細胞 (medium-sized spiny neuron)に連絡していることが明らかになってきた。
本研究では、ラットの視床から背外側前方および後方線条体への入力を逆行性ウイルスベクターによって遺伝子標識し、それぞれの標識回路を選択的に機能操作したモデル動物を用いて聴覚弁別学習課題を実施した。その結果、視床ー背外側前方線条体ネットワークが重要学習獲得に必須の役割を果たすことを明らかにした。

Current Status of Research Progress

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

Reason

背外側前方線条体と視床との神経連絡を選択的に経路標識して、その神経機能操作を行なったモデル動物を作出し、聴覚性弁別学習課題を実施した。昨年度は実験動物数が少なかったが、今年度は統計解析にも十分耐えうる数の動物数での実験を行い、データの確からしさを得ることができた。
一方、背外側後方線条体と視床のネットワークには上記に見られる学習行動への寄与はないことも見出した。

Strategy for Future Research Activity

弁別学習行動中の前背外側線条体および視床における神経活動記録実験の進行と記録データの解析方法を検討する。

Research Products

• [Journal Article] Protocol for highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence in rodents (2023)
  • Author(s): Matsushita Natsuki、Kato Shigeki、Nishizawa Kayo、Sugawara Masateru、Takeuchi Kosei、Miyasaka Yoshiki、Mashimo Tomoji、Kobayashi Kazuto
  • Journal Title: STAR Protocols Volume: 4 Issue: 4 Pages: 102667-102667
  • DOI: 10.1016/j.xpro.2023.102667
  • Peer Reviewed / Open Access
• [Journal Article] Reward expectation enhances action-related activity of nigral dopaminergic and two striatal output pathways (2023)
  • Author(s): Rios Alain、Nonomura Satoshi、Kato Shigeki、Yoshida Junichi、Matsushita Natsuki、Nambu Atsushi、Takada Masahiko、Hira Riichiro、Kobayashi Kazuto、Sakai Yutaka、Kimura Minoru、Isomura Yoshikazu
  • Journal Title: Communications Biology Volume: 6 Issue: 1 Pages: 914-914
  • DOI: 10.1038/s42003-023-05288-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anatomical identification of a corticocortical top-down recipient inhibitory circuitry by enhancer-restricted transsynaptic tracing (2023)
  • Author(s): Atsumi Yusuke、Oisi Yasuhiro、Odagawa Maya、Matsubara Chie、Saito Yoshihito、Uwamori Hiroyuki、Kobayashi Kenta、Kato Shigeki、Kobayashi Kazuto、Murayama Masanori
  • Journal Title: Frontiers in Neural Circuits Volume: 17 Pages: 1245097-1245097
  • DOI: 10.3389/fncir.2023.1245097
  • Peer Reviewed / Open Access
• [Journal Article] Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive drinking behavior (2023)
  • Author(s): Takemoto Makoto、Kato Shigeki、Kobayashi Kazuto、Song Wen-Jie
  • Journal Title: iScience Volume: 26 Issue: 6 Pages: 106985-106985
  • DOI: 10.1016/j.isci.2023.106985
  • Peer Reviewed / Open Access
• [Journal Article] 1. Reinstating olfactory bulb derived limbic gamma oscillations alleviates depression. (2023)
  • Author(s): Li, Q.*, Takeuchi, Y.*, Wang, J., Barcsai, L., Pedraza, L.K., Kozak, G., Nakai, S., Kato, S., Kobayashi, K., Ohsawa, M., Lorincz, M.L., Devinsky, O., Buzsaki, G. and Berenyi, A. * Equal contribution
  • Journal Title: Neuron Volume: In press Issue: 13 Pages: 1-11
  • DOI: 10.1016/j.neuron.2023.04.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 2. Highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence. (2023)
  • Author(s): Matsushita, N.*, Kato, S.*, Nishizawa, K., Sugawara, M., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K. * Equal contribution
  • Journal Title: Cell Rep. Methods Volume: 3 Issue: 2 Pages: 100393-100393
  • DOI: 10.1016/j.crmeth.2022.100393
  • Peer Reviewed / Open Access
• [Journal Article] 3. Catecholaminergic cell type-specific expression of Cre recombinase in knock-in transgenic rats generated by the Combi-CRISPR technology. (2022)
  • Author(s): Matsushita, N., Nishizawa, K., Kato, S., Iguchi, Y., Fukabori, R., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K.
  • Journal Title: J. Neurosci. Methods Volume: 381 Pages: 109707-109707
  • DOI: 10.1016/j.jneumeth.2022.109707
  • Peer Reviewed / Open Access
• [Journal Article] 4. Recording and manipulation of the maternal oxytocin neural activities in mice. (2022)
  • Author(s): Yukinaga, H., Hagihara, M., Tsujimoto, K., Chiang, H., Kato, S., Kobayashi, K. and Miyamichi, K.
  • Journal Title: Curr. Biol. Volume: 32 Issue: 17 Pages: 1-9
  • DOI: 10.1016/j.cub.2022.06.083
  • Peer Reviewed / Open Access
• [Journal Article] Thalamostriatal System Controls the Acquisition, Performance, and Flexibility of Learning Behavior (2021)
  • Author(s): Kato Shigeki、Nishizawa Kayo、Kobayashi Kazuto
  • Journal Title: Frontiers in Systems Neuroscience Volume: 15 Pages: 729389-729389
  • DOI: 10.3389/fnsys.2021.729389
  • Peer Reviewed / Open Access
• [Journal Article] Chemogenetic inactivation reveals the inhibitory control function of the prefronto-striatal pathway in the macaque brain (2021)
  • Author(s): Oguchi Mineki、Tanaka Shingo、Pan Xiaochuan、Kikusui Takefumi、Moriya-Ito Keiko、Kato Shigeki、Kobayashi Kazuto、Sakagami Masamichi
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 1088-1088
  • DOI: 10.1038/s42003-021-02623-y
  • Peer Reviewed / Open Access
• [Journal Article] Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projection. (2021)
  • Author(s): Otsuka Y, Tsuge H, Uezono S, Tanabe S, Fujiwara M, Miwa M, Kato S, Nakamura K, Kobayashi K, Inoue K, Takada M
  • Journal Title: Viruses Volume: 13(7) Issue: 7 Pages: 1387-1387
  • DOI: 10.3390/v13071387
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons (2020)
  • Author(s): Fukabori R, Iguchi Y, Kato S, Takahashi K, Eifuku S, Tsuji S, Hazama A, Uchigashima M, Watanabe M, Mizuma H, Cui Y, Onoe H, Hikishima K, Yasoshima Y, Osanai M, Inagaki R, Fukunaga K, Nishijo T, Momiyama T, Benton R, & Kobayashi K
  • Journal Title: The Journal of Neuroscience Volume: 40 Issue: 43 Pages: 8367-8385
  • DOI: 10.1523/jneurosci.1720-20.2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dopaminergic signaling in the nucleus accumbens modulates stress-coping strategies during inescapable stress. (2020)
  • Author(s): Cui, W., Aida, T., Ito, H., Kobayashi, K., Wada, Y., Kato, S., Nakano, T., Zhu, M., Isa, K., Kobayashi, K., Isa, T., Tanaka, K. and Aizawa, H.
  • Journal Title: J Neurosci. Volume: 40 Issue: 38 Pages: 7241-7254
  • DOI: 10.1523/jneurosci.0444-20.2020
  • NAID: 120007170786
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pseudotyped lentiviral vectors for tract-targeting and application for the functional control of selective neural circuits. (2020)
  • Author(s): Kato, S. and Kobayashi, K.
  • Journal Title: J Neurosci. Methods Volume: 344 Pages: 108854-108854
  • DOI: 10.1016/j.jneumeth.2020.108854
  • Peer Reviewed
• [Journal Article] Macaques Exhibit Implicit Gaze Bias Anticipating Others’ False-Belief-Driven Actions via Medial Prefrontal Cortex (2020)
  • Author(s): Hayashi Taketsugu、Akikawa Ryota、Kawasaki Keisuke、Egawa Jun、Minamimoto Takafumi、Kobayashi Kazuto、Kato Shigeki、Hori Yukiko、Nagai Yuji、Iijima Atsuhiko、Someya Toshiyuki、Hasegawa Isao
  • Journal Title: Cell Reports Volume: 30 Issue: 13 Pages: 4433-4444
  • DOI: 10.1016/j.celrep.2020.03.013
  • Peer Reviewed / Open Access
• [Journal Article] The Emergence of a Stable Neuronal Ensemble from a Wider Pool of Activated Neurons in the Dorsal Medial Prefrontal Cortex during Appetitive Learning in Mice (2019)
  • Author(s): Brebner Leonie S.、Ziminski Joseph J.、Margetts-Smith Gabriella、Sieburg Meike C.、Reeve Hayley M.、Nowotny Thomas、Hirrlinger Johannes、Heintz Tristan G.、Lagnado Leon、Kato Shigeki、Kobayashi Kazuto、Ramsey Leslie A.、Hall Catherine N.、Crombag Hans S.、Koya Eisuke
  • Journal Title: The Journal of Neuroscience Volume: 40 Issue: 2 Pages: 395-410
  • DOI: 10.1523/jneurosci.1496-19.2019
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 神経ネットワーク機能操作のための遺伝学的介入 (2024)
  • Author(s): 加藤 成樹
  • Organizer: 2023年度 第15回脳科学クラスター・ミニリトリート
  • Invited
• [Presentation] Corticostriatal input and behavioral habituation (2023)
  • Author(s): Shigeki KATO, Nozomu YOSHIOKA and Kazuto KOBAYASHI
  • Organizer: 第46回日本神経科学大会
  • Invited
• [Presentation] 組換え酵素依存的遺伝子発現スイッチシステムにおけるリーク発現抑制型ベクター (2023)
  • Author(s): 加藤 成樹, 松下 夏樹, 小林 和人
  • Organizer: 第46回日本分子生物学会
• [Presentation] Thalamostriatal input in learning behavior cued by auditory stimuli (2022)
  • Author(s): Shigeki KATO and Kazuto KOBAYASHI
  • Organizer: 第45回日本神経科学大会
• [Presentation] 聴覚性弁別学習行動における視床線条体入力の役割 (2022)
  • Author(s): 加藤 成樹, 小林 和人
  • Organizer: 第45回日本分子生物学会
• [Presentation] Input analysis to striatal subdivision with high-frequency retrograde viral vector (2021)
  • Author(s): 加藤 成樹, 小林 和人
  • Organizer: 第44回日本神経科学大会
• [Presentation] 線条体subdivisionへの入力解析と行動機能操作 (2021)
  • Author(s): 加藤 成樹, 小林 和人
  • Organizer: 第44回日本分子生物学会
• [Presentation] Comparative analysis of retrograde gene transduction efficiency between various modified virus types. (2020)
  • Author(s): 加藤 成樹, 小林 和人
  • Organizer: 第43回日本神経科学大会
• [Book] Neuromethods (2022)
  • Author(s): Kenta Kobayashi, Shigeki Kato, and Kazuto Kobayashi(分担執筆)
  • Total Pages: 331
  • Publisher: Humana Press
  • ISBN: 9781071629178
• [Book] 決定版 ウイルスベクターによる遺伝子導入実験ガイド (2020)
  • Author(s): 平井宏和、日置寛之、小林和人
  • Total Pages: 281
  • Publisher: 羊土社
  • ISBN: 9784758122474