Studies on molecular mechanisms that control development and function of the neural network

• Project/Area Number: 17002016
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: NAKANISHI Shigetada Osaka Bioscience Institute, 所長 (20089105)
• Co-Investigator(Kenkyū-buntansha): OKAZAWA Makoto (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (40414130) ; KIWADA Tatsuto (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (50414131) ; HIKIDA Takatoshi (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (70421378) ; DOI Tomokazu (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (20435564) ; YAWATA Satoshi (財)大阪バイオサイエンス研究所, システムズ生物学部門, 研究員 (90455246)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥647,400,000 (Direct Cost: ¥498,000,000、Indirect Cost: ¥149,400,000); Fiscal Year 2009: ¥129,480,000 (Direct Cost: ¥99,600,000、Indirect Cost: ¥29,880,000); Fiscal Year 2008: ¥129,480,000 (Direct Cost: ¥99,600,000、Indirect Cost: ¥29,880,000); Fiscal Year 2007: ¥129,480,000 (Direct Cost: ¥99,600,000、Indirect Cost: ¥29,880,000); Fiscal Year 2006: ¥129,480,000 (Direct Cost: ¥99,600,000、Indirect Cost: ¥29,880,000); Fiscal Year 2005: ¥129,480,000 (Direct Cost: ¥99,600,000、Indirect Cost: ¥29,880,000)
• Keywords: 小脳 / 大脳基底核 / 運動記憶 / 報酬・忌避記憶 / 薬物依存 / 神経回路 / 発達 / 神経伝達 / 基底核 / 神経ネットワーク / 記憶 / 運動

Research Abstract

This project established a novel technique that allowed selective and reversible blockade of specific transmission in the network. The studies using this technique unraveled sequential and integrative processes of acquisition, expression and storage of motor learning at different cerebellar circuits and distinct roles of two parallel pathways of the basal ganglia in rewardbased and aversive learning. This project also disclosed a novel mechanism that controls the activity-dependent maturing processes of the functional cerebellar network organization.

Research Products

• [Journal Article] Ca2+-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation (2009)
  • Author(s): Nakajima, Y., Mochida, S., Okawa, K, Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 18385-18389
  • Peer Reviewed
• [Journal Article] Role of calcineurin signaling in membrane potential-regulated maturation of cerebellar granule cells (2009)
  • Author(s): Okazawa, M., Abe, H., Katsukawa, M., Iijima, K., Kiwada, T., Nakanishi, S.
  • Journal Title: J. Neurosci. 29 Pages: 2938-2947
  • Peer Reviewed
• [Journal Article] Ectopic synaptic ribbons in dendrites of mouse retinal ON-and OFF-bipolar cells (2009)
  • Author(s): Ishii, M.et al.
  • Journal Title: Cell Tissue Res. 338 Pages: 355-375
  • Peer Reviewed
• [Journal Article] Ca^<2+>-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation (2009)
  • Author(s): Nakajima, Y.et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 18385-18389
  • Peer Reviewed
• [Journal Article] Isolation of ON bipolar cell-specific genes (2009)
  • Author(s): Nakajima, Y.et al.
  • Journal Title: J.Biochemistry 29 Pages: 2938-2947
  • Peer Reviewed
• [Journal Article] Genetic manipulation study of information processing in the cerebellum (2009)
  • Author(s): Nakanishi, S.
  • Journal Title: Neuroscience 162 Pages: 723-731
  • Peer Reviewed
• [Journal Article] Role of calcineurin signaling in membrane potential-regulated Maturation of cerebellar granule cells (2009)
  • Author(s): Okazawa, M.et al.
  • Journal Title: J.Neurosci. 29 Pages: 2939-2947
  • Peer Reviewed
• [Journal Article] The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival (2009)
  • Author(s): Lee, H.et al.
  • Journal Title: Brain Res. 1249 Pages: 244-250
  • Peer Reviewed
• [Journal Article] The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival (2009)
  • Author(s): Lee,H., et al.
  • Journal Title: Brain Res. 1249 Pages: 244-250
  • Peer Reviewed
• [Journal Article] Role of calcineur in signaling in membrane potential-regulated maturation of cerebellar granule cells (2009)
  • Author(s): Okazawa, M., et al.
  • Journal Title: J. Neurosci 29 Pages: 2938-2947
  • Peer Reviewed
• [Journal Article] Dual regulation of NR2B and NR2C expression by NMDA receptor activation in mouse cerebellar granule cell cultures (2008)
  • Author(s): Iijima, K., Abe, H., Okazawa, M., Moriyoshi, K., Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 105 Pages: 12010-12015
  • Peer Reviewed
• [Journal Article] Dual regulation of NR2B and NR2C expression NMDA receptor activation in mouse cerebellar granule cell cultures (2008)
  • Author(s): Iijima, K.,et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 12010-12015
  • Peer Reviewed
• [Journal Article] Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission (2007)
  • Author(s): Wada, N., Kishimomto, Y., Watanabe, D., Kano, M., Hirano, T., Funabiki, K., Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 16690-16695
  • Peer Reviewed
• [Journal Article] Crystal Structures of autoinhibitory PDZ domain of Tamalin: Implications for metabotropic glutamate receptor trafficking regulation (2007)
  • Author(s): Sugi, T., Oyama, T., Muto, T., Nakanishi, S., Morikawa, K. & Jingami, H.
  • Journal Title: EMBO Journal 26 Pages: 2206-2217
• [Journal Article] A novel connection between rods and ON cone bipolar cells revealed by ectopic metabotropic glutamate receptor 7(mGluR7) in mGluR6-deficient mouse retinas. (2007)
  • Author(s): Tsukamoto, T., Morigiwa, K., Ishii, M., Takao, M., Iwatsuki, K. Nakanishi, S. & Fukuda, Y.
  • Journal Title: Journal of Neuroscience 27 Pages: 6261-6267
• [Journal Article] GABA (A) receptor-mediated signaling alters the structure of spontaneous activiry in the developing retina. (2007)
  • Author(s): Wan, C-T., Blankenship, A., Elstoritt, J., Flkhman, J., Nakanishi, S. & Feller, M.
  • Journal Title: Journal of Neuroscience 27 Pages: 9130-9140
• [Journal Article] Altered sensitivities to morphine and cocaine in scaffolod protein tamalin knockout mice. (2007)
  • Author(s): Ogawa, M., Nakamura, K., Kitano, J., Furushima, K., Kiyonari H., Nakayama, R., Nakao, K. & Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 14789-14794
• [Journal Article] Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission. (2007)
  • Author(s): Wada, N., Kishimoto, Y., Watanabe, D., Kano, J., Hirano, T., Funabiki, K. & Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 16690-16695
• [Journal Article] Membrane potential-regulated Ca2+ signaling in development and maturation of cerebellar granule cells (2006)
  • Author(s): Nakanishi, S., Okazawa, M.
  • Journal Title: J. Physiol. 575 Pages: 389-395
  • Peer Reviewed
• [Journal Article] Membrane potential-regulated Ca^<2+> signaling in development and maturation of cerebellar granule cells (2006)
  • Author(s): Nakanishi, S, Okazawa, M.
  • Journal Title: Journal of Physiology 575 Pages: 389-395
• [Journal Article] Molecular mechanisms of intercellular communication in the hormonal and neural systems (2006)
  • Author(s): Nakanishi, S.
  • Journal Title: IUBMB Life 58 Pages: 349-357
• [Journal Article] Expression profile of BDNF-responsive genes during cerebellar granule cell development (2006)
  • Author(s): Sato, M., Suzuki, K., Nakanishi, S.
  • Journal Title: Biochem.Biophys.Res.Commun. 341・2 Pages: 304-309
• [Journal Article] Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway (2006)
  • Author(s): Rene, C.R., Tian, N., Gang, J., Nakanishi, S., Stryker, M.P., Copenhagen, D.R.
  • Journal Title: Journal of Neuroscience 26・46 Pages: 11857-11869
• [Journal Article] Serine racemase binds to PICK1 : Potential Relevance to Schizophrenia (2006)
  • Author(s): Fujii, K., Maeda, K., Hikida, I., Mustata, A.K., Balkissoon, R., Xia, J., Yamada, T., Kawahara, R., Okawa, M., Huganir, R.L., Ujike, H., Snyder, S.H., Sawa, A.
  • Journal Title: Molecular Psychiatry 11 Pages: 150-157
• [Journal Article] Expression profile of BDNF-responsive genes during cerebellar granule cell development (2006)
  • Author(s): Sato, M.
  • Journal Title: Biochem.Biophys.Res.Commun. 341・2 Pages: 304-309
• [Journal Article] Neuronal depolarization controls brain-derived neurotrophic factor-induced upregulation of NR2C NMDA receptor via calcineurin signaling (2005)
  • Author(s): Suzuki, K., Sato, M., Morishima, Y., Nakanishi, S.
  • Journal Title: J. Neurosci. 25 Pages: 9535-9543
  • Peer Reviewed
• [Journal Article] A pivotal role of calcineurin signaling in development and maturation of postnatal cerebellar granule cells (2005)
  • Author(s): Sato, M., Suzuki, K., Yamazaki, H., Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 5874-5894
  • Peer Reviewed
• [Journal Article] Enhanced cocaine responsiveness and impaired motor coordination in metabotropic gluamate receptor subtype 2 knockout mice (2005)
  • Author(s): Morishima, Y., Miyakawa, T., Furuyashiki, T., Tanaka, Y., Mizuma, H., Nakanishi, S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 4170-4175
  • Peer Reviewed
• [Journal Article] Synaptic mechanisms of the cerebellar cortical network (2005)
  • Author(s): Nakanishi, S.
  • Journal Title: Trends Neurosci. 28 Pages: 93-100
  • Peer Reviewed
• [Journal Article] Synaptic mechanisms of the cerebellar cortical network (2005)
  • Author(s): Nakanishi, S.
  • Journal Title: Trends in Neuroscience 28・2 Pages: 93-100
• [Journal Article] Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice (2005)
  • Author(s): Morishima, Y.
  • Journal Title: Proc.Natl.Acad.Sci. USA 102・11 Pages: 4170-4175
• [Journal Article] A pivotal role of calcineurin signaling in development and maturation of postnatal cerebellar granule cells (2005)
  • Author(s): Sato, M.
  • Journal Title: Proc.Natl.Acad.Sci. USA 102・16 Pages: 5874-5897
• [Journal Article] Opposite effects of Zn on the in vitro binding of [3H]LY354740 to recombinant and native metabotropic glutamate 2 and 3 receptors (2005)
  • Author(s): Malherbe, P.
  • Journal Title: J.Neurochem. 94・1 Pages: 150-160
• [Journal Article] Neuronal Depolarization Controls Brain-Derived Neurotrophic Factor-Induced Upregulation of NR2C NMDA Receptor via Calcineurin Signaling (2005)
  • Author(s): Suzuki, K
  • Journal Title: J.Neurosci. 25・41 Pages: 9535-9543
• [Journal Article] Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior
  • Author(s): Hikida, T., Kimura, K., Wada, N., Funabiki, K., Nakanishi, S. Neuron
  • Journal Title: (in press)
  • Peer Reviewed
• [Journal Article] Genetic manipulation study of information processing in the cerebellum.
  • Author(s): Nakanishi S.
  • Journal Title: Neuroscience (in press)
  • Peer Reviewed
• [Journal Article] Identification of ON bipolar cell-specific genes
  • Author(s): Nakajima, Y., et al.
  • Journal Title: J. Biochem. (in press)
  • Peer Reviewed
• [Journal Article] Crystal structures of autoinhibitory PDZ domain of Tamalin : Implications for metabotropic glutamate receptor trafficking regulation
  • Author(s): Sugi, T., Oyama, T., Muto, T., Nakanishi, S., Morikawa, K., Jingami, H.
  • Journal Title: EMBO Journal (in press)
• [Presentation] Understanding the glutamatergic networks (2010)
  • Author(s): Shigetada Nakanishi
  • Organizer: Neurobiology : From Molecules to Systems
  • Place of Presentation: Montpellier, France
  • Year and Date: 2010-02-09
• [Presentation] Information processing and integration of motor learning in the cerebellar circuitry (2010)
  • Author(s): Shigetada Nakanishi
  • Organizer: IBRO Pre-conference satellite meeting : Functional Architecture and operational principles of cortical networks
  • Place of Presentation: Pecs, Hungary
  • Year and Date: 2010-01-20
• [Presentation] Integrative and regulatory mechanisms of synaptic transmission in the neural network. (2009)
  • Author(s): Nakanishi, S.
  • Organizer: Key-note lecture, Gordon Research Conference: Neural Circuits & Plasticity
  • Place of Presentation: Salve Regina University, Newport, USA
  • Year and Date: 2009-06-07
• [Presentation] Integrative and regulatory mechanisms of synaptic transmission in the neural network (2009)
  • Author(s): Shigetada Nakanishi
  • Organizer: Gordon Conference : Neural Circuits & Plasticity
  • Place of Presentation: New Port, USA
  • Year and Date: 2009-06-07
• [Presentation] Integrative and regulatory synaptic mechanisms of the cerebellar network. (2008)
  • Author(s): Nakanishi, S.
  • Organizer: The Welcome Trust and Cold Spring Harbor Laboratory joint conference on‘Integrative Approaches to Brain Complexity
  • Place of Presentation: Wellcome Trust Conference Centre, Cambridge, UK
  • Year and Date: 2008-10-02
• [Presentation] Integrative and regulatory synaptic mechanisms of the cerebellar network (2008)
  • Author(s): Shigetada Nakanishi
  • Organizer: Cold Spring Harbor Laboratory Integrative Approaches to Brain Complexity Meeting
  • Place of Presentation: Cambridge,UK
  • Year and Date: 2008-10-02
• [Presentation] Function and signaling mechanism of the mGluR-interacting scaffold tamalin. (2008)
  • Author(s): Nakanishi, S.
  • Organizer: The 6th International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Taormina, Sicily, Italy.
  • Year and Date: 2008-09-14
• [Presentation] Function and signaling mechanism of the mGluR-interacting scaffld tamalin (2008)
  • Author(s): Shigetada Nakanishi
  • Organizer: The 6th International Meeting on Metabotropic Glutamate Receptors
  • Place of Presentation: Taormina, Sicily, Italy
  • Year and Date: 2008-09-14
• [Presentation] The neural network: integration and regulation of synaptic transmission. (2007)
  • Author(s): Nakanishi, S.
  • Organizer: Gruber Prize lecture, Neuroscience 2007
  • Place of Presentation: San Diego Convention Center, San Diego, USA.
  • Year and Date: 2007-11-04
• [Presentation] The neural network: integration and regulation of synaptic transmission (2007)
  • Author(s): Nakanishi, S.
  • Organizer: Neuroscience 2007
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-04
• [Presentation] Integrative and regulatory mechanisms of synaptic transmission in the neural network. (2007)
  • Author(s): Nakanishi, S.
  • Organizer: Key-note lecture, ASPET The Third GPCR Colloquium
  • Place of Presentation: Washington DC Convention Center, Washing ton DC, USA.
  • Year and Date: 2007-04-28
• [Presentation] Integrative and regulatory mechanisms of synaptic transmission in the neural network (2007)
  • Author(s): Nakanishi, S.
  • Organizer: ASPET The Third GPCR Colloquium
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2007-04-28
• [Book] The History of Neuroscience in Autobiography (2009)
  • Author(s): Nakanishi, S.
  • Publisher: Oxford University Press
• [Book] The History of Neuroscience in Autobiography (2009)
  • Author(s): Shigetada Nakanishi
  • Total Pages: 576
  • Publisher: Oxford University Press
• [Book] The History of Neuroscience in Autobiography
  • Author(s): Nakanishi, S.
  • Publisher: Oxford University Press(In press)
• [Remarks]
  • URL: http://www.obi.or.jp/index.html
• [Remarks]
  • URL: http://www.obi.or.jp/
• [Patent(Industrial Property Rights)] 大脳基底核神経回路の神経伝達を解析する方法 (2010)
  • Inventor(s): 疋田貴俊、中西重忠
  • Industrial Property Rights Holder: 財団法人大阪バイオサイエンス研究所
  • Filing Date: 2010-04-30