Analysys of local circuit mechanisms in the basal forebrain in terms of parvalbumin and acetylcholine

• Project/Area Number: 17K07063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Momiyama Toshihiko 東京慈恵会医科大学, 医学部, 教授 (20230055)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 大脳基底核 / 前脳基底核 / アセチルコリン / パルブアルブミン / シナプス伝達 / ムスカリン受容体 / マウス / IPSCs / GABA / M1受容体 / 光感受性色素 / パッチクランプ / 光遺伝学 / 線条体 / MSNs / チャネルロドプシン / スライス / シナプス

Outline of Final Research Achievements

A whole-cell patch-clamp study was carried out to elucidate the GABAergic synaptic transmission from medium-spiny neurons (MSNs) to cholinergic neurons (ChNs), using transgenic mice expressing light-sensitive channel rhodopsin 2. Light-evoked GABAergic inhibitory postsynaptic currents (IPSCs) were inhibited by activation M1 musacarinic acetylcholine receptors. Further analyses suggest that the inhibition is presynaptic origin, and that considerable proportion of the presynaptic M1 receptors regulating GABA release locate on intracellular organelle.

Academic Significance and Societal Importance of the Research Achievements

本課題で焦点を当てた中枢ニューロン・シナプスは、随意運動機能および認知機能を制御する中枢であり、その病的状態であるパーキンソン病およびアルツハイマー病の発症機構に密接に関与している。たとえばパーキンソン患者は65歳以上の1％に存在し、また、アルツハイマー型を含む認知症は高齢化社会における喫緊の課題といえる。本研究成果が上記生理機能の機構および疾患の発症機構解明ひいては新たな治療法の開発につながることを期待したい。

Research Products

• [Journal Article] M1 muscarinic acetylcholine receptor-mediated inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons (2021)
  • Author(s): Suzuki E & Momiyama T
  • Journal Title: European Journal of Neuroscience Volume: 53 Issue: 3 Pages: 796-813
  • DOI: 10.1111/ejn.15074
  • Peer Reviewed
• [Journal Article] Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility. (2020)
  • Author(s): Hayase Y, Amano S, Hashizume K, Tominaga T, Miyamoto H, Kanno Y, Ueno-Inoue Y, Inoue T, Yamada M, Ogata S, Balan S, Hayashi K, Miura Y, Tokudome K, Ohno Y, Nishijo T, Momiyama T, Yanagawa Y, Takizawa A, Mashimo T, Serikawa T, Sekine A, Nakagawa E, Takeshita E, Yoshikawa T, Waga C, Inoue K, Goto YI, Nabeshima Y, et al.
  • Journal Title: Acta Neuropathol Commun. Volume: 8 Issue: 1 Pages: 206-206
  • DOI: 10.1186/s40478-020-01082-6
  • 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] De novo PHACTR1 mutations in West syndrome and their pathophysiological effects (2018)
  • Author(s): Hamada Nanako、Ogaya Shunsuke、Nakashima Mitsuko、Nishijo Takuma、Sugawara Yuji、Iwamoto Ikuko、Ito Hidenori、Maki Yuki、Shirai Kentaro、Baba Shimpei、Maruyama Koichi、Saitsu Hirotomo、Kato Mitsuhiro、Matsumoto Naomichi、Momiyama Toshihiko、Nagata Koh-ichi
  • Journal Title: Brain Volume: 141 Pages: 3098-3114
  • DOI: 10.1093/brain/awy246
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Grafted Miniature-Swine Neural Stem Cells of Early Embryonic Mesencephalic Neuroepithelial Origin can Repair the Damaged Neural Circuitry of Parkinson's Disease Model Rats. (2018)
  • Author(s): Mine Y, Momiyama T, Hayashi T & Kawase T.
  • Journal Title: Neuroscience Volume: 386 Pages: 51-67
  • DOI: 10.1016/j.neuroscience.2018.06.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dopamine and serotonin-induced modulation of GABAergic and glitamatergic transmission in the striatum and basal forebrain (2017)
  • Author(s): Momiyama T & Nishijo T
  • Journal Title: Frontiers in Neuroanatomy Volume: 42 Pages: 11-11
  • Peer Reviewed / Open Access
• [Presentation] 5-HT1A and 5-HT1B receptor-mediated inhibition of glutamatergic synaptic transmission onto rat basal forebrain cholinergic neurones. (2021)
  • Author(s): Momiyama T, Nishijo T & Suzuki E
  • Organizer: 第126回日本解剖学会総会・全国学術集会第98回日本生理学会大会 合同大会
• [Presentation] Presynaptic inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons in young-adult mice. (2021)
  • Author(s): Suzuki e & Momiyama T
  • Organizer: 第94 回日本薬理学会年会
• [Presentation] Inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons by presynaptic M1 receptor activation. (2020)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: 第43 回日本神経科学学会
• [Presentation] Inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons by presynaptic muscarine receptor activation in adult mice (2020)
  • Author(s): Momiyama T & Suzuki E
  • Organizer: 12th FENS Forum
  • Int'l Joint Research
• [Presentation] M1ムスカリン受容体による線条体中型有棘細胞からコリン作動性介在ニューロンへのGABA放出抑制 (2020)
  • Author(s): 鈴木江津子、籾山俊彦
  • Organizer: 第93回日本薬理学会年会
• [Presentation] 線条体中型有棘細胞からコリン作動性介在ニューロンへのGABA放出のM1ムスカリン受容体によるシナプス前抑制 (2020)
  • Author(s): 籾山俊彦。鈴木江津子
  • Organizer: 第97回日本生理学会大会
• [Presentation] 線条体中型有棘神経からコリン作動性介在ニューロンへのGABA遊離はM1アセチルコリン受容体によりシナプス前性に抑制される (2019)
  • Author(s): 鈴木江津子、籾山俊彦
  • Organizer: 第42回日本神経科学大会
• [Presentation] 5-HTによる前脳基底核コリン作動性ニューロンへの興奮性伝達に対するCav2.1依存的な抑制 (2019)
  • Author(s): 西條琢真、籾山俊彦
  • Organizer: 第92回日本薬理学会年会（大阪）
• [Presentation] M1 receptor-mediated presynaptic inhibition of IPSCs in basal forebrain cholinergic neurons (2019)
  • Author(s): Momiyama T & Nishijo T
  • Organizer: 9th FAOPS Congress (Kobe)
  • Int'l Joint Research
• [Presentation] 5-HT-induced inhibition of excitatory transmission onto basal forebrain cholinergic neurons (2019)
  • Author(s): Nishijo T & Momiyama T
  • Organizer: 9th FAOPS Congress (Kobe)
  • Int'l Joint Research
• [Presentation] Both 5-HT1A and 5-HT1B receptoe-mediated inhibition of glutamatergic transmission onto cholinergic neuron in basal forebrain (2018)
  • Author(s): Nishijo T & Momiyama T
  • Organizer: WCP2018 Kyoto
  • Int'l Joint Research
• [Presentation] Presynaptic modulation of GABAergic transmission onto striatal cholinergic interneuron by M1 acetylcholine receptor activation (2018)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: WCP2018 Kyoto
  • Int'l Joint Research
• [Presentation] Presynaptic modulation of GABAergic transmission onto striatal cholinergic interneurons by M1 muscarinic receptor activation (2018)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: 11th FENS Forum of Neuroscience (Berlin)
  • Int'l Joint Research
• [Presentation] Serotonin-induced bP/Q-type calcium channel-dependent inhibition of excitatory transmission onto basal forebrain cholinergic neurons (2018)
  • Author(s): Nishijo T & Momiyama T
  • Organizer: 11th FENS Forum of Neuroscience (Berlin)
  • Int'l Joint Research
• [Presentation] Modulation of glutamatergic transmission onto basal forebrain cholinergic neurons by serotonin (2018)
  • Author(s): Nishijo T & Momiyama T
  • Organizer: Neuroscience 2018 (Kobe)
• [Presentation] M1 muscarinic receptors presynaptically inhibit GABAergic transmission from striatal medium spiny neurons onto cholinergic interneurons (2018)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: Neuroscience 2018 (Kobe)
• [Presentation] M1 receptor-mediated presynaptic inhibition of GABAergic transmission fron striatal medium spiny neurons onto cholinergic interneurons. (2018)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: 第95回日本生理学会大会
• [Presentation] Postsynaptic G-protein cascade is not required for the inhibitory cholinergic modulation of GABAergic transmission onto striatal cholinergic interneurons. (2017)
  • Author(s): Suzuki E & Momiyama T
  • Organizer: 第40回日本神経科学大会
• [Presentation] Serotonin-induced pre- and postsynaptic inhibition of glutamatergic transmission onto basal forebrain cholinergic neurons. (2017)
  • Author(s): Nishijo T & Momiyama T
  • Organizer: 第40回日本神経科学大会