線条体におけるカルシウム振動の描出と生理学的意義の解明

2017 Fiscal Year Annual Research Report

• Project Area: Non-linear Neuro-oscillology: Towards Integrative Understanding of Human Nature
• Project/Area Number: 16H01621
• Research Institution: Keio University
• Principal Investigator: 田中 謙二 慶應義塾大学, 医学部(信濃町), 准教授 (30329700)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 意欲 / 線条体 / 島皮質 / D2 / カルシウム

Outline of Annual Research Achievements

意欲行動中に見られる線条体D2-MSNの活動振動がどのような神経入力によって作られるのか調べるために、腹外側線条体D2-MSNの入力先の一つの候補である島皮質の投射神経の活動を調べた。線条体へ投射する島皮質神経軸索の集合カルシウム観察では、トライアル開始時に終末のカルシウム信号が低下すること、線条体D2-MSNはトライアル開始に集合カルシウムが増加することから、島皮質の活動抑制が線条体D2-MSNの興奮をもたらしていることがわかった。この異なる活動を説明するには、両者の間に抑制性の介在神経が存在することが予想される。PV陽性GABA介在神経の集合カルシウム活動を意欲行動中に計測したところ、トライアル開始時に活動が抑制されなかった。このことからPV陽性介在神経以外の介在神経、例えばneuropeptide Y陽性、tyrosine hydroxylase陽性などのGABA介在神経が島皮質-線条体のfeedforward inhibitionを担当していることが示唆された。
更に、ドパミン神経入力が線条体投射神経の集合カルシウム濃度を支配しているか調べた。線条体D1-MSNだけにカルシウムセンサーを発現するマウスを樹立し、意欲行動中の活動を調べた。その結果、線条体D1-MSNは、D2-MSNと同じく、意欲行動の開始時に集合カルシウム濃度が増加した。意欲行動の開始時にドパミン神経からのドパミン放出が起こることが知られている。ドパミンはD1受容体へは活動亢進を、D2受容体へは活動抑制をもたらすので、ドパミン入力が線条体MSNの集合カルシウム濃度を変化させている可能性が低いことがわかった。
以上の結果から、意欲行動中の線条体MSNの活動振動は主に大脳皮質からの入力によって作られることがわかった。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Texas, Austin/University of Pittsburg/University of Miami(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: University of Texas, Austin/University of Pittsburg/University of Miami
  • # of Other Institutions: 1
• [Int'l Joint Research] University of Ottawa(Canada)
  • Country Name: Canada
  • Counterpart Institution: University of Ottawa
• [Int'l Joint Research] Universite Libre de Bruxelles(Belgium)
  • Country Name: Belgium
  • Counterpart Institution: Universite Libre de Bruxelles
• [Journal Article] A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing (2018)
  • Author(s): Murakami Tatsuya C.、Mano Tomoyuki、Saikawa Shu、Horiguchi Shuhei A.、Shigeta Daichi、Baba Kousuke、Sekiya Hiroshi、Shimizu Yoshihiro、Tanaka Kenji F.、Kiyonari Hiroshi、Iino Masamitsu、Mochizuki Hideki、Tainaka Kazuki、Ueda Hiroki R.
  • Journal Title: Nat Neurosci Volume: 21 Pages: 627-637
  • DOI: 10.1038/s41593-018-0109-1
  • Peer Reviewed
• [Journal Article] Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics. (2018)
  • Author(s): Chen S, Weitemier AZ, Zeng X, He L, Wang X, Tao Y, Huang AJY, Hashimotodani Y, Kano M, Iwasaki H, Parajuli LK, Okabe S, Teh DBL, All AH, Tsutsui-Kimura I, Tanaka KF, Liu X, McHugh TJ.
  • Journal Title: Science Volume: 359 Pages: 679-684
  • DOI: 10.1126/science.aaq1144.
  • Peer Reviewed
• [Journal Article] Aberrant astrocyte Ca2+ signals “AxCa signals” exacerbate pathological alterations in an Alexander disease model (2018)
  • Author(s): Saito Kozo、Shigetomi Eiji、Yasuda Rei、Sato Ryuichi、Nakano Masakazu、Tashiro Kei、Tanaka Kenji F.、Ikenaka Kazuhiro、Mikoshiba Katsuhiko、Mizuta Ikuko、Yoshida Tomokatsu、Nakagawa Masanori、Mizuno Toshiki、Koizumi Schuichi
  • Journal Title: Glia Volume: 66 Pages: 1053～1067
  • DOI: 10.1002/glia.23300
  • Peer Reviewed
• [Journal Article] Role of Purinergic Receptor P2Y1 in Spatiotemporal Ca2+ Dynamics in Astrocytes. (2018)
  • Author(s): Shigetomi E, Hirayama YJ, Ikenaka K, Tanaka KF, Koizumi S.
  • Journal Title: J Neurosci. Volume: 38 Pages: 1383-1395
  • DOI: 10.1523/JNEUROSCI.2625-17.2017
  • Peer Reviewed
• [Journal Article] Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network. (2017)
  • Author(s): Good JM, Mahoney M, Miyazaki T, Tanaka KF, Sakimura K, Watanabe M, Kitamura K, Kano M.
  • Journal Title: Cell Rep Volume: 21 Pages: 2066-2073
  • DOI: doi: 10.1016/j.celrep.2017.10.101.
  • Peer Reviewed / Open Access
• [Journal Article] Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior. (2017)
  • Author(s): Vahid-Ansari F, Daigle M, Manzini MC, Tanaka KF, Hen R, Geddes SD, Beique JC, James J, Merali Z, Albert PR.
  • Journal Title: J Neurosci. Volume: 37 Pages: 11967-11978
  • DOI: 10.1523/JNEUROSCI.1668-17.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice. (2017)
  • Author(s): Watabe T, Xu M, Watanabe M, Nabekura J, Higuchi T, Hori K, Sato MP, Nin F, Hibino H, Ogawa K, Masuda M, Tanaka KF.
  • Journal Title: Sci Rep Volume: 7 Pages: -
  • DOI: 10.1038/s41598-017-13997-7.
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination. (2017)
  • Author(s): Yano R, Hata J, Abe Y, Seki F, Yoshida K, Komaki Y, Okano H, Tanaka KF.
  • Journal Title: Neurochem Int Volume: S0197-0186 Pages: 30350-30359
  • DOI: 10.1016/j.neuint.2017.10.004
  • Peer Reviewed
• [Journal Article] Hearing Loss Controlled by Optogenetic Stimulation of Nonexcitable Nonglial Cells in the Cochlea of the Inner Ear. (2017)
  • Author(s): Sato MP, Higuchi T, Nin F, Ogata G, Sawamura S, Yoshida T, Ota T, Hori K, Komune S, Uetsuka S, Choi S, Masuda M, Watabe T, Kanzaki S, Ogawa K, Inohara H, Sakamoto S, Takebayashi H, Doi K, Tanaka KF, Hibino H.
  • Journal Title: Front Mol Neurosci Volume: 10 Pages: -
  • DOI: 10.3389/fnmol.2017.00300.
  • Peer Reviewed / Open Access
• [Journal Article] Distinct Roles of Ventromedial versus Ventrolateral Striatal Medium Spiny Neurons in Reward-Oriented Behavior. (2017)
  • Author(s): Tsutsui-Kimura I, Natsubori A, Mori M, Kobayashi K, Drew MR, de Kerchove d'Exaerde A, Mimura M, Tanaka KF.
  • Journal Title: Curr Biol Volume: 27 Pages: 3042-3048
  • DOI: 10.1016/j.cub.2017.08.061
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mitochondrial DNA Double-Strand Breaks in Oligodendrocytes Cause Demyelination, Axonal Injury, and CNS Inflammation. (2017)
  • Author(s): Madsen PM, Pinto M, Patel S, McCarthy S, Gao H, Taherian M, Karmally S, Pereira CV, Dvoriantchikova G, Ivanov D, Tanaka KF, Moraes CT, Brambilla R.
  • Journal Title: J Neurosci. Volume: 37 Pages: 10185-10199
  • DOI: 10.1523/JNEUROSCI.1378-17.2017.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor. (2017)
  • Author(s): Imada T, Nakamura S, Hisamura R, Izuta Y, Jin K, Ito M, Kitamura N, Tanaka KF, Mimura M, Shibuya I, Tsubota K.
  • Journal Title: Sci Rep Volume: 7 Pages: -
  • DOI: 10.1038/s41598-017-06022-4.
  • Peer Reviewed / Open Access
• [Journal Article] High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates. (2017)
  • Author(s): Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue KI, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H.
  • Journal Title: Neuron Volume: 94 Pages: 1085-1100
  • DOI: 10.1016/j.neuron.2017.05.017.
  • Peer Reviewed
• [Journal Article] Association of impaired neuronal migration with cognitive deficits in extremely preterm infants. (2017)
  • Author(s): Kubo KI, Deguchi K, Nagai T, Ito Y, Yoshida K, Endo T, Benner S, Shan W, Kitazawa A, Aramaki M, Ishii K, Shin M, Matsunaga Y, Hayashi K, Kakeyama M, Tohyama C, Tanaka KF, Tanaka K, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, Nakajima K.
  • Journal Title: JCI Insight Volume: 2 Pages: -
  • DOI: 10.1172/jci.insight.88609
  • Peer Reviewed / Open Access
• [Journal Article] OCD candidate gene SLC1A1/EAAT3 impacts basal ganglia-mediated activity and stereotypic behavior. (2017)
  • Author(s): Zike ID, Chohan MO, Kopelman JM, Krasnow EN, Flicker D, Nautiyal KM, Bubser M, Kellendonk C, Jones CK, Stanwood G, Tanaka KF, Moore H, Ahmari SE, Veenstra-VanderWeele J.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114 Pages: 5719-5724
  • DOI: 10.1073/pnas.1701736114.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1 Receptor Downregulation. (2017)
  • Author(s): Shinozaki Y, Shibata K, Yoshida K, Shigetomi E, Gachet C, Ikenaka K, Tanaka KF, Koizumi S.
  • Journal Title: Cell Rep Volume: 19 Pages: 1151-1164
  • DOI: 10.1016/j.celrep.2017.04.047.
  • Peer Reviewed / Open Access
• [Journal Article] A New Paradigm for Evaluating Avoidance/Escape Motivation. (2017)
  • Author(s): Tsutsui-Kimura I, Bouchekioua Y, Mimura M, Tanaka KF.
  • Journal Title: Int J Neuropsychopharmacol. Volume: 20 Pages: 593-601
  • DOI: 10.1093/ijnp/pyx031.
  • Peer Reviewed / Open Access
• [Journal Article] The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model. (2017)
  • Author(s): Shimizu T, Wisessmith W, Li J, Abe M, Sakimura K, Chetsawang B, Sahara Y, Tohyama K, Tanaka KF, Ikenaka K.
  • Journal Title: Glia Volume: 65 Pages: 917-930
  • DOI: 10.1002/glia.23134.
  • Peer Reviewed
• [Journal Article] Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity. (2017)
  • Author(s): Natsubori A, Tsutsui-Kimura I, Nishida H, Bouchekioua Y, Sekiya H, Uchigashima M, Watanabe M, de Kerchove d'Exaerde A, Mimura M, Takata N, Tanaka KF.
  • Journal Title: J Neurosci Volume: 37 Pages: 2723-2733
  • DOI: 10.1523/JNEUROSCI.3377-16.2017.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 強迫症研究のこれからtranslational researchの可能性について (2017)
  • Author(s): 15.酒井 雄希, 田中 謙二
  • Journal Title: 精神科治療学 Volume: 32 Pages: 399-404
• [Presentation] 光観察と光操作を組み合わせた意欲行動研究 (2017)
  • Author(s): 田中謙二
  • Organizer: 第2回 ルミノジェネティクス研究会
  • Invited
• [Presentation] Oligodendrocyte is a dynamic modulator of conduction velocity (2017)
  • Author(s): 田中謙二、山崎良彦
  • Organizer: 第60回 日本神経化学会
• [Presentation] 島皮質-線条体回路と意欲行動 (2017)
  • Author(s): 田中謙二
  • Organizer: 第5回 心身医学のニューロサイエンス研究会
  • Invited
• [Presentation] 光操作・光計測 (2017)
  • Author(s): 田中謙二
  • Organizer: 第49回藤田学園医学会・研究最前線セミナー
  • Invited
• [Presentation] Fiberphotometry (2017)
  • Author(s): 田中謙二
  • Organizer: 第28回 マイクロダイアリシス研究会
  • Invited
• [Presentation] 意欲行動の開始を支配する島皮質-線条体回路 (2017)
  • Author(s): 田中謙二
  • Organizer: 次世代脳 新学術領域合同シンポジウム
  • Invited
• [Remarks] 柔軟な行動選択を行う脳内メカニズムの発見
  • URL: https://www.keio.ac.jp/ja/press-releases/2017/9/29/28-24433/