Obsessive compulsive disorder-related striosome circuits in the striatum

• Project/Area Number: 21500362
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: AOSAKI Toshihiko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (70221033)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 強迫行為 / 線条体ストリオソーム / ドーパミン / シナプス可塑性 / 常同行動 / 皮質線条体路

Research Abstract

The striatal striosome compartment is considered one of the critical stations related to obsessive compulsive disorder. Medium spiny projection neurons in the striosomes but not in the matrix have mu-opioid receptors whose physiological roles have not fully examined. We found that prior blockade of muscarinic receptors augmented the suppressive effect of the mu-opioid receptor agonist DAMGO on the inhibitory postsynaptic currents. This phenomenon suggests the notion that the cessation of tonic action potential discharges of cholinergic interneurons in the striatum(the pause response of the tonically active cholinergic neurons of the striatum) during behavioral learning induces disinhibition of neuronal activities of the striosomal medium spiny neurons which are believed to encode motivational information.

Research Products

• [Journal Article] Imbalanced suppression of excitatory and inhibitory synaptic transmission onto mouse striatal projection neurons during start of anesthesia induction with sevoflurane in vitro. (2012)
  • Author(s): Ose, Y., Miura, M., Inoue, R., Andou, N., Aosaki, T., Nishimura, K.
  • Journal Title: European Journal of Neuroscience Volume: 35 Issue: 9 Pages: 1396-1405
  • DOI: 10.1111/j.1460-9568.2012.08065.x
  • Peer Reviewed
• [Journal Article] The suppressive effect of μ-opioid receptors on GABAergic IPSC is modulated by alteration of PKC activity via muscarinic receptors in striosomes of the mouse striatum (2012)
  • Author(s): Inoue, R., Aosaki, T., Miura, M.
  • Journal Title: NeuroReport Volume: 23(3) Issue: 3 Pages: 184-188
  • DOI: 10.1097/wnr.0b013e32834faab0
  • Peer Reviewed
• [Journal Article] 和文総説:「パーキンソン病におけるコリン作動性ニューロン」 (2012)
  • Author(s): 三浦正巳、井上律子、青崎敏彦
  • Journal Title: Clinical Neuroscience Volume: 30 Pages: 697-699
• [Journal Article] パーキンソン病におけるコリン作動性ニューロン (2012)
  • Author(s): 三浦正巳、井上律子、青崎敏彦
  • Journal Title: Clinical Neuroscience Volume: 30(印刷中)
• [Journal Article] Imbalanced suppression of excitatory and inhibitory synaptic transmission onto mouse striatal projection neurons during start of anesthesia induction with sevoflurane in vitro (2012)
  • Author(s): Ose, Y., Miura, M., Inoue, R., Andou, N., Aosak, T., Nishimura, K.
  • Journal Title: European Journal of Neuroscience Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] The suppressive effect of μ-opioid receptors on GABAergic IPSC is modulated by alteration of PKC activity via muscarinic receptors in striosomes of the mouse striatum (2012)
  • Author(s): Inoue, R., Aosaki, T., Miura, M.
  • Journal Title: NeuroReport Volume: 23(3) Pages: 184-188
  • Peer Reviewed
• [Journal Article] Postnatal development of tyrosine hydroxylase mRNAexpressing neurons in mouse neostriatum (2011)
  • Author(s): Masuda M, Miura M, Inoue R, Imanishi M, Saino-Saito S, Takada M, Kobayashi K, Aosaki T
  • Journal Title: Eur J Neurosci Volume: 34 Issue: 9 Pages: 1355-1367
  • DOI: 10.1111/j.1460-9568.2011.07873.x
  • Peer Reviewed
• [Journal Article] Usp46, encoding a ubiquitin specific peptidase, is a quantitative trait gene underlying “behavioral despair” in mice (2010)
  • Author(s): Ebihara, S., Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K.,Yoshimura, T., Nabeshima, T.
  • Journal Title: Sleep and Biological Rhythms Volume: 8（2） Issue: 2 Pages: 114-119
  • DOI: 10.1111/j.1479-8425.2010.00435.x
  • Peer Reviewed
• [Journal Article] Activin Bi-directionally Controls the Fate of Fear Memory (2010)
  • Author(s): Ageta, H., Ikegami, S., Miura, M., Masuda, M., Migishima, R., Hino, T., Takashima, N., Murayama, A., Sugino, H., Setou, M., Kida, S., Yokoyama, M., Yoshihisa Hasegawa, Y., Tsuchida, K., Aosaki, T., Inokuchi, K.
  • Journal Title: Learning and Memory Volume: 17 Issue: 4 Pages: 176-185
  • DOI: 10.1101/lm.16659010
  • Peer Reviewed
• [Journal Article] Acetylcholine-dopamine balance hypothesis in the striatum: an update (2010)
  • Author(s): Aosaki, T., Miura, M., Suzuki, T., Nishimura, K. and Masuda, M.
  • Journal Title: Geriatrics and Gerontology International Volume: 10(Suppl.1) Issue: s1 Pages: 148-157
  • DOI: 10.1111/j.1447-0594.2010.00588.x
  • NAID: 10027273560
• [Journal Article] Usp46, encoding a ubiquitin specific peptidase, is a quantitative traitgene underlying "behavioral despair" in mice. (2010)
  • Author(s): Ebihara, S., Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K., Yoshimura, T., Nabeshima, T.
  • Journal Title: Sleep and Biological Rhythms Volume: 8(2) Pages: 114-119
  • Peer Reviewed
• [Journal Article] Activin Bi-directionally Controls the Fate of Fear Memory. (2010)
  • Author(s): Ageta, H., Ikegami, S., Miura, M., Masuda, M., Migishima, R., Hino, T., Takashima, N., Murayama, A., Sugino, H., Setou, M., Kida, S., Yokoyama, M., Yoshihisa Hasegawa, Y., Tsuchida, K., Aosaki, T., Inokuchi, K.
  • Journal Title: Learning and Memory Volume: 17 Pages: 176-185
  • Peer Reviewed
• [Journal Article] Acetylcholine-dopamine balance hypothesis in the striatum : anupdate. (2010)
  • Author(s): Aosaki, T., Miura, M., Suzuki, T., Nishimura, K., Masuda, M.
  • Journal Title: Geriatrics and Gerontology International Volume: 10(Supp1.1)
• [Journal Article] Roles of cholinergic interneurons in inter-compartmental communication and synaptic plasticity in the striatum. (2010)
  • Author(s): Aosaki, T., Miura, M.
  • Journal Title: The Journal of Physiological Sciences Volume: 60(Supp1.1)
• [Journal Article] Effects of the volatile anesthetic sevoflurane on presynaptic and postsynaptic activities of the mouse striatal neurons (2010)
  • Author(s): Ose, Y., Miura, M., Inoue, R., Aosaki, T., Nishimura, K.
  • Journal Title: Neuroscience Research Volume: 68(Supp1.1) Pages: 428-428
• [Journal Article] マウヌ線条体チロシンヒドロキシラーゼmRNA陽性細胞の生理学的性質 (2010)
  • Author(s): 青崎敏彦、増田正雄、三浦正巳、今西美智子、井上律子、齋野・齋藤幸子、高田昌彦、小林和人
  • Journal Title: 基礎老化研究 Volume: 34(2) Pages: 21-21
• [Journal Article] 中枢神経系におけるドーパミン受容体のはたらき (2009)
  • Author(s): 三浦正巳、増田正雄、青崎敏彦
  • Journal Title: 生体の科学 Volume: 60(5) Pages: 4123-413
  • URL: http://ej.islib.jp/ejournal/2425100895.html?
• [Journal Article] Identification of Usp46, encoding a ubiquitin specific peptidase, as a quantitative trait gene regulating mouse immobile behavior in the tail suspension test and the forced swimming test (2009)
  • Author(s): Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K., Yoshimura, T., Nabeshima, T., Ebihara, S.
  • Journal Title: Nature Genetics Volume: 41(6) Issue: 6 Pages: 688-695
  • DOI: 10.1038/ng.344
  • Peer Reviewed
• [Journal Article] Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice (2009)
  • Author(s): Sato, T., Miura, M., Yamada, M., Yoshida, T., Wood, J.D., Yazawa, I., Masuda, M., Suzuki, T., Shin, R-M., Yau, H-J., Liu, F-C., Shimohata, T., Onodera, O., Ross, C.A., Katsuki, M., Takahashi, H., Kano, M., Aosaki, T., Tsuji, S.
  • Journal Title: Human Molecular Genetics Volume: 18(4) Issue: 4 Pages: 723-736
  • DOI: 10.1093/hmg/ddn403
  • Peer Reviewed
• [Journal Article] 線条体におけるアセチリコリンとドーパミンの生理的相互作用 (2009)
  • Author(s): 青崎敏彦、三浦正巳、増田正雄
  • Journal Title: Brain and Nerve Volume: 61(4) Pages: 373-380
  • URL: http://ej.islib.jp/ejournal/1416100461.html?
• [Journal Article] Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice (2009)
  • Author(s): Sato, T., Miura, M., Yamada, M., Yoshida, T., Wood, J.D., Yazawa, I., Masuda, M., Suzuki, T., Shin, R-M., Yau, H-J., Liu, F-C., Shimohata, T., Onodera, O, Ross, C.A., Katsuki, M., Takahashi, H., Kano, M., Aosaki, T., Tsuji, S.
  • Journal Title: Human Molecular Genetics 18 Pages: 723-736
  • Peer Reviewed
• [Journal Article] Identification of Usp46, encoding a ubiquitin specific peptidase, as a quantitative trait gene regulating mouse immobile behavior in the tail suspension test and the forced swimming test. (2009)
  • Author(s): Tomida, S., Mamiya, T., Sakamaki, H., Miura, M., Aosaki, T., Masuda, M., Niwa, M., Kameyama, T., Kobayashi, J., Iwaki, Y., Imai, S., Ishikawa, A., Abe, K., Yoshimura, T., Nabeshima, T., Ebihara, S.
  • Journal Title: Nature Genetics 41 Pages: 688-695
  • Peer Reviewed
• [Journal Article] 中枢神経系におけるドーパミン受容体のはたらき (2009)
  • Author(s): 三浦正巳、増田正雄、青崎敏彦
  • Journal Title: 生体の科学 60 Pages: 412-413
• [Journal Article] 線条体におけるアセチリコリンとドーパミンの生理的相互作用 (2009)
  • Author(s): 三浦正巳、増田正雄、青崎敏彦
  • Journal Title: Brian and Nerve特集「大脳基底核-分子基盤から臨床まで」 61 Pages: 373-380
• [Presentation] Postnatal development of intrinsic tyrosine hydroxylase mRNA-expressing neurons in the striatum (2012)
  • Author(s): Toshihiko Aosaki, Masao Masuda, Masami Miura, Ritusko Inoue
  • Organizer: 第85回日本薬理学会年会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2012-03-28
• [Presentation] ニコチン受容体の脱感作は線条体コリン作動性ニューロンへのGABA入力を調節する (2012)
  • Author(s): 三浦正巳、井上律子、青崎敏彦
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本文化会館
• [Presentation] Postnatal development of intrinsic tyrosine hydroxylase mRNA-expressing neurons in the striatum (2012)
  • Author(s): Toshihiko Aosaki, Masao Masuda, Masami Miura, Ritusko Inoue
  • Organizer: 第85回日本薬理学会年会シンポジウム28
  • Place of Presentation: 京都
• [Presentation] ニコチン受容体の脱感作は線条体コリン作動性ニューロンへのGABA入力を調節するDesensitization of nicotinic receptor modulates GABAergic inputs to cholinergic interneurons in the matrix of mouse striatum (2012)
  • Author(s): 三浦正巳、井上律子、青崎敏彦
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野県松本文化会館
• [Presentation] Suppressive effect on GABAergic IPSC viaμ-opioid receptor is modulated by endogenous acetylcholine in the mouse striatum (2011)
  • Author(s): Ritsuko Inoue, Masami Miura, Toshihiko Aosaki
  • Organizer: The Society for Neuroscience 41st Annual Meeting
  • Place of Presentation: Washington, D. C., USA
• [Presentation] 「μオピオイド受容体作動薬と内在性アセチルコリンがマウス線条体のGABA作動性抑制電流に与える影響」Neuro2011 (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 「線条体チロシン水酸化酵素mRNA陽性細胞の分類と生後発達」JBAGS (2011)
  • Author(s): 増田正雄、三浦正巳、今西美知子、齋野・斉藤幸子、井上律子、高田昌彦、小林和人、青崎敏彦
  • Organizer: 第26回日本大脳基底核研究会
  • Place of Presentation: 神奈川県・箱根町・パレスホテル箱根
• [Presentation] マウス線条体におけるμオピオイド受容体の効果に内在性アセチルコリンが及ぼす影響 (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: 第34回日本基礎老化学会大会
  • Place of Presentation: 東京
• [Presentation] アセチルコリンはマウス線条体の抑制性電流に対するμオピオイド受容体の抑制効果を減弱する (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: 第88回日本生理学会大会
  • Place of Presentation: 横浜
• [Presentation] マウス線条体におけるμオピオイド受容体の効果に内在性アセチルコリンが及ぼす影響Endogenous acetylcholine attenuates the μ-opioid receptor-induced suppression of GABAergic IPSC in mouse striatum (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: 第34回日本基礎老化学会大会
  • Place of Presentation: 東京
• [Presentation] 線条体チロシン水酸化酵素mRNA陽性細胞の分類と生後発達 (2011)
  • Author(s): 増田正雄、三浦正巳、今西美知子、齋野・斉藤幸子、井上律子、高田昌彦、小林和人、青崎敏彦
  • Organizer: JBAGS第26回日本大脳基底核研究会
  • Place of Presentation: 神奈川県・箱根町・パレスホテル箱根
• [Presentation] μオピオイド受容体作動薬と内在性アセチルコリンがマウス線条体のGABA作動性抑制電流に与える影響Opposite effects of the μ-opioid receptor agonist DAMGO and endogenous acetylcholine on GABAergic IPSC in mouse striatum (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: Neuro2011、第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Suppressive effect on GABAergic IPSC via μ-opioid receptor is modulated by endogenous acelylcholine in the mouse striatum (2011)
  • Author(s): Ritsuko Inoue, Masami Miura, Toshihiko Aosaki
  • Organizer: The Society for Neuroscience 41st Annual Meeting
  • Place of Presentation: Washington, D.C., USA
• [Presentation] アセチルコリンはマウス線条体の抑制性電流に対するμオピオイド受容体の抑制効果を減弱する Suppressive effect of μ-opipid receptors on GABAergic IPSC is attenuated by endogenous acetylcholine via muscarinic receptors in mouse striatum (2011)
  • Author(s): 井上律子、三浦正巳、青崎敏彦
  • Organizer: 第88回日本生理学大会
  • Place of Presentation: 横浜市(震災の影響により誌上発表に変更)
• [Presentation] 東京農工大学大学院修士課程講義 (2010)
  • Author(s): 青崎敏彦
  • Organizer: 環境老年学特論II:パーキンソン病の発症メカニズム
  • Place of Presentation: 東京
  • Year and Date: 2010-07-13
• [Presentation] 環境老年学持論II:パーキンソン病の発症メカニズム (2010)
  • Author(s): 青崎敏彦
  • Organizer: 東京農工大学大学院修士課程講義
  • Place of Presentation: 東京
  • Year and Date: 2010-07-13
• [Presentation] 自治医大時代 (2010)
  • Author(s): 青崎敏彦
  • Organizer: 木村實先生定年退職記念講演会「視覚、大脳基底核研究から異分野統合的脳研究へ」
  • Place of Presentation: 京都
  • Year and Date: 2010-05-22
• [Presentation] 自治医大時代 (2010)
  • Author(s): 青崎敏彦
  • Organizer: 木村寛先生定年退職記念講演会「視覚、大脳基底核から異分野統合的脳研究へ」
  • Place of Presentation: 京都
  • Year and Date: 2010-05-22
• [Presentation] 線条体コンパートメント間相互作用におけるコリナージックニューロンの役割とシナプス可塑性への関与 Roles of cholinergic interneurons in inter-compartmental communication and synaptic plasticity in the striatum (2010)
  • Author(s): 青崎敏彦、三浦正巳
  • Organizer: 第87回日本生理学会大会シンポジウム31「ドーパミン伝達による脳内ネットワークと可塑性・学習の制御 Dopamine-mediated regulation of brain network and plasticity
  • Place of Presentation: 盛岡市
  • Year and Date: 2010-05-20
• [Presentation] 「吸入麻酔薬セボフルレンのマウス線条体ニューロンに対する作用」Neuro2010 (2010)
  • Author(s): 大瀬善之、三浦正巳、井上律子、青崎敏彦、西村欣也
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸
• [Presentation] マウス線条体チロシンヒドロキシラーゼmRNA陽性細胞の生理学的性質 (2010)
  • Author(s): 青崎敏彦、増田正雄、三浦正巳、今西美智子、井上律子、齋野・齋藤幸子、高田昌彦、小林和人
  • Organizer: 日本基礎老化学会第33回大会
  • Place of Presentation: 名古屋
• [Presentation] 線条体におけるアセチリコリンとドーパミンの生理的相互作用とシナプス可塑性 (2010)
  • Author(s): 青崎敏彦
  • Organizer: 平成22年度生理学研究所研究会
  • Place of Presentation: 岡崎
• [Presentation] Roles of cholinergic interneurons in inter-compartmental communication and synaptic plasticity in the striatum (2010)
  • Author(s): Aosaki, T., Miura, M
  • Organizer: The Journal of Physiological Sciences
  • Place of Presentation: 盛岡
• [Presentation] 線条体におけるアセチリコリンとドーパミンの生理的相互作用とシナプス可塑性 (2010)
  • Author(s): 青崎敏彦
  • Organizer: 平成22年度生理学会研究所研究会「シナプス可塑性の動作原理」
  • Place of Presentation: 岡崎
• [Presentation] 吸入麻酔薬セボフルレンのマウス線条体ニューロンに対する作用 Effects of the volatile anesthetic sevoflurane on presynaptic and postsynaptic activitiesof the mouse striatalneurons (2010)
  • Author(s): 大瀬善之、三浦正巳、井上律子、青崎敏彦、西村欣也
  • Organizer: Neuro2010、第33回日本神経科学大会
  • Place of Presentation: 神戸
• [Presentation] 環境老年学特論II:パーキンソン病の発症メカニズム (2009)
  • Author(s): 青崎敏彦
  • Organizer: 東京農工大学大学院修士課程講義
  • Place of Presentation: 東京
  • Year and Date: 2009-07-07
• [Presentation] パーキンソン病のしくみと治療の最前線 (2009)
  • Author(s): 青崎敏彦
  • Organizer: 当事者と介護者のための特別講演会,主催わかな会
  • Place of Presentation: 川崎市麻生区
  • Year and Date: 2009-04-18
• [Presentation] パーキンソン病のしくみと治療の最前線 (2009)
  • Author(s): 青崎敏彦
  • Organizer: 当事者と介護者のための特別講演会、主催わかな会(パーキンソン病友の会あさお)
  • Place of Presentation: 川崎市麻生区
  • Year and Date: 2009-04-18
• [Presentation] Roles of cholinergic interneurons in inter-compartmental communication and synaptic plasticity in the striatum (2009)
  • Author(s): Aosaki, T
  • Organizer: Satellite Symposiumof the 32nd Annual Meeting of the Japan Neuroscience Society The Basal Ganglia in Health and Disease
  • Place of Presentation: シンポジウム
• [Presentation] 動物のメンタリティーを測定する (2009)
  • Author(s): 青崎敏彦
  • Organizer: 第105・106回老年学公開講座
• [Presentation] 線条体コリン作動性インターニューロンのGABA性入力の調節機構 (2009)
  • Author(s): 三浦正巳、増田正雄、青崎敏彦
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] GABA性の抑制低下とうつ病様行動異常 (2009)
  • Author(s): 三浦正巳、富田滋、間宮隆吉、酒巻大岳、増田正雄、丹羽美苗、亀山勉、小林淳哉、井脇有香、今井早希、石川明、安部訓也、吉村崇、鍋島俊隆、海老原史樹文、青崎敏彦
  • Organizer: 日本基礎老化学会第32回大会
  • Place of Presentation: 横浜
• [Presentation] GABA性の抑制低下とうつ病様行動異常 (2009)
  • Author(s): 三浦正巳、富田滋、間宮隆吉、酒巻大岳、増田正雄、丹羽美苗、亀山勉、小林淳哉、井脇有香、今井早希、石川明、安部訓也、吉村崇、鍋島俊隆、海老原史樹文、青崎敏彦
  • Organizer: 日本基礎老化学会第32回大会OS-11、6学会合同ポスター合P-15
  • Place of Presentation: 横浜
• [Presentation] Roles of cholinergic interneurons in inter-compartmental communication and synaptic plasticity in the striatum (2009)
  • Author(s): 青崎敏彦
  • Organizer: Satellite Symposium of the 32^<nd> Annual Meeting of the Japan Neuroscience Society "The Basal Ganglia in Health and Disease"
  • Place of Presentation: Okazaki
• [Presentation] 線条体コリン作動性インターニューロンのGABA性入力の調節機構 (2009)
  • Author(s): 三浦正巳、増田正雄、青崎敏彦
  • Organizer: 第32回日本神経科学大会P3-a30
  • Place of Presentation: 名古屋
• [Remarks]
  • URL: http://www.tmig.or.jp/
• [Remarks]
  • URL: http://www.tmig.or.jp
• [Remarks]
  • URL: http://www.tmig.or.jp
• [Remarks]
  • URL: http://www.tmig.or.jp