Neural circuit mechanisms underlying behavioral control through corticostriatal pathways in an area- and input-specific manner

• Project/Area Number: 18H02545
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Kobayashi Kazuto 福島県立医科大学, 医学部, 教授 (90211903)
• Co-Investigator(Kenkyū-buntansha): 西澤 佳代 福島県立医科大学, 医学部, 助教 (30644108) ; 瀬戸川 将 福島県立医科大学, 医学部, 博士研究員 (30760508) ; 加藤 成樹 福島県立医科大学, 医学部, 准教授 (90443879)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 経路選択的操作 / 細胞標的法 / 化学遺伝学 / オペラント学習 / 皮質線条体路

Outline of Final Research Achievements

In this project, we aim to analyze the behavioral functions of corticotriatal neurons, focusing on the projections arising from the motor cortex and auditory cortex. ＳSelective neural pathway targeting and chemogenetic suppression indicated the importance of M1 corticostriatal neurons in the formation of habitual behavior. Selective elimination of PT type neurons appeared to reduce the habit formation, and the analysis of the effect of IT type ablation is in progress. In addition, 18FDG-PET and electrophysiological recording experiments showed the increased brain activity in the posterior ventrolateral striatum (pVLS) during the late phase of auditory discrimination. Retrograde axonal tracing from this region indicated dense innervation from the secondary auditory cortex and insular cortex to the pVLS. The behavioral and physiological roles of these corticostriatal neurons will be clarified in the future.

Academic Significance and Societal Importance of the Research Achievements

大脳皮質と基底核を結ぶネットワークは、学習の獲得、実行、行動切り替えなどさまざまな行動制御に関わることが知られているが、それぞれの皮質領野から線条体に入力する経路の役割や異なる投射特性を持つIT型・PT型ニューロンの機能の相違についてはほとんど研究が進んでいない。これらの多様な特性を持つ皮質線条体ニューロンの機能を明らかにすることは学術的な意義が深い。また、皮質線条体路の異常は、統合失調症、注意多動性障害、依存などの精神疾患の病態と深く関連することから、これらの経路の生理機能の理解は精神疾患の病態解明や治療法の開発に繋がる可能性がある。

Research Products

• [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: Journal of Neuroscience Methods Volume: 344 Pages: 108854-108854
  • DOI: 10.1016/j.jneumeth.2020.108854
  • Peer Reviewed
• [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 (2020)
  • 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: J Neurosci. Volume: 40 Pages: 395-410
  • DOI: 10.1523/jneurosci.1496-19.2019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impaired cortico-striatal excitatory transmission triggers epilepsy (2020)
  • Author(s): Miyamoto Hiroyuki、Tatsukawa Tetsuya、Shimohata Atsushi、Yamagata Tetsushi、Suzuki Toshimitsu、Amano Kenji、Mazaki Emi、Raveau Matthieu、Ogiwara Ikuo、Oba-Asaka Atsuko、Hensch Takao K.、Itohara Shigeyoshi、Sakimura Kenji、Kobayashi Kenta、Kobayashi Kazuto、Yamakawa Kazuhiro
  • Journal Title: Nat Commun Volume: 10 Pages: 1-13
  • DOI: 10.1038/s41467-019-09954-9
  • Peer Reviewed / Open Access
• [Journal Article] Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus. (2019)
  • Author(s): Nobuyuki Sakayori, Shigeki Kato, Masateru Sugawara, Susumu Setogawa, Hotaka Fukushima, Rie Ishikawa, Satoshi Kida, Kazuto Kobayashi
  • Journal Title: Mol Brain Volume: 12 Issue: 13 Pages: 1-12
  • DOI: 10.1186/s13041-019-0431-x
  • Peer Reviewed / Open Access
• [Journal Article] Task-dependent function of striatal cholinergic interneurons (2018)
  • Author(s): Okada K, Nishizawa K, Setogawa S, Hashimoto K, Kobayashi K.
  • Journal Title: Eur J Neurosci Volume: - Issue: 10 Pages: 1174-1183
  • DOI: 10.1111/ejn.13768
  • Peer Reviewed
• [Journal Article] Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents. (2018)
  • Author(s): Tainaka K. Murakami TC, Susaki EA, Shimizu C, Saito R, Takahashi K, Hayashi-Takagi A, Sekiya H, Arima Y, Nojima S, Ikemura M, Ushiku T, Shimizu Y, Murakami M, Tanaka KF, Iino M, Kasai H, Sasaoka T. Kobayashi K, Miyazono K, Morii E, Isa T, Fukayama M, Kakita A. Ueda HR.
  • Journal Title: Cell Reports Volume: 24 Pages: 2196-2210
  • DOI: 10.1016/j.celrep.2018.07.056
  • NAID: 120006542018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monitoring and updating of action selection for goal-directed behavior through the striatal direct and indirect pathways (2018)
  • Author(s): Nonomura S, Nishizawa K, Sakai Y, Kawaguchi Y, Kato S, Uchigashima M, Watanabe M, Yamanaka K, Enomoto K, Chiken S, Sano H, Soma S, Yoshida J, Samejima K, Ogawa M, Kobayashi K, Nambu A, Isomura Y, Kimura M
  • Journal Title: Neuron Volume: 99(6) Issue: 6 Pages: 1302-1314
  • DOI: 10.1016/j.neuron.2018.08.002
  • NAID: 120006869035
  • Peer Reviewed / Open Access
• [Presentation] 認知運動スキルの獲得を支える大脳基底核の神経回路シフト (2020)
  • Author(s): 瀬戸川将、小林和人
  • Organizer: 第７５回日本体力医学会
• [Presentation] The individual history of reward learning and stress responsibility: resilience induced by contingency learning between action and reward (2020)
  • Author(s): Iguchi, Y., Hikishima, K., & Kobayashi, K
  • Organizer: The 43rd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Role of parietal cortex in the perception of movement (2020)
  • Author(s): Megumi Fukuda, Maya Odagawa, Yasuhiro Oishi, Chie Matsubara, Shigeki Kato, Kazuto Kobayashi, Katsumi Watanabe, Masanori Murayama
  • Organizer: The 43rd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Thalamostriatal system controlling learning and behavioral flexibility (2019)
  • Author(s): Kazuto Kobayashi
  • Organizer: 28th International Conference on Neuroscience and Neurochemistry
  • Int'l Joint Research / Invited
• [Presentation] Different function of striatal sub-regions during acquisition of the auditory discrimination task (2019)
  • Author(s): Susumu Setogawa, Takashi Okauchi, Di Hu, Nobuyuki Sakayori, Mika Shigeta, Keigo Hikishima, Hirotaka Onoe, Yilong Cui, Kazuto Kobayashi
  • Organizer: 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Behavioral regulation through molecular genetic manipulation of selective neural circuit (2019)
  • Author(s): Shigeki Kato, Masateru Sugawara, Kazuto Kobayashi
  • Organizer: 42nd Annual Meeting of the Japan Neuroscience Society
• [Presentation] Behavioral selection and switching flexibility regulated by thalamustriatal circuit (2018)
  • Author(s): Shigeki Kato, Kazuto Kobayashi
  • Organizer: The 41st Annual Meeting of the Japan Neuroscience Society
• [Presentation] Identification of indirect pathway neurons and dopaminergic innervation in the rat dorsomedial striatum (2018)
  • Author(s): Satoshi Nonomura, Shigeki Kato, Yoshio Iguchi, Kayo Nishizawa, Yutaka Sakai, Yasuo Kawaguchi, Atsushi Nambu, Masahiko Watanabe, Kazuto Kobayashi, Yoshikazu Isomura, Minoru Kimura
  • Organizer: The 41st Annual Meeting of the Japan Neuroscience Society
• [Presentation] 神経回路の遺伝子操作による動物モデル研究 (2018)
  • Author(s): 小林 和人
  • Organizer: 第２９回東北動物実験研究会
  • Invited