Compartment specific modulation with intrinsic acetylcholine in the dorsal and caudal striatum of mice

• Project/Area Number: 16K01957
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Miura Masami 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, 研究副部長 (40291091)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アセチルコリン / オピオイド / ドーパミン / 大脳基底核 / 線条体 / 機能領域 / 恐怖条件付け

Outline of Final Research Achievements

Cholinergic interneurons substantially regulate physiological functions of the striatum. We investigated the ionic mechanisms controlling the neural activity of the cholinergic neurons and the regional effects of nicotinic receptors on synaptic transmissions in the caudal striatum. Excitatory glutamatergic inputs to the cholinergic neurons were suppressed by high frequency stimulation in conjunction with an agonist of mu opioid receptors. The prolonged suppression was eminent in the medial part of the striatum and disturbed by an α4β2 nAChR antagonist, suggesting the involvement of intrinsic acetylcholine. The synergistic effect of acetylcholine and opioid was heterogeneously observed with medio-lateral axes. Considering the synergistic effect of opioid and intrinsic acetylcholine on the synaptic plasticity there might be a regional diversity in the effect of acetylcholine on the reinforcement learning and adaptive behaviors.

Academic Significance and Societal Importance of the Research Achievements

線条体は、運動から行動、情動といった多くの機能を担っている。そのため多くの疾患にも関わる。ドーパミンやアセチルコリンは線条体の強力な調節因子であるが、線条体全てに強く作用してしまうため、運動だけ、あるいは行動異常だけを治療することは困難である。。機能領域に特異的な生理的、薬理的作用が分かれば、特定の機能だけを調節できる可能性がある。新たな治療法のために役立つ情報といえる。

Research Products

• [Journal Article] Modulation of hyperpolarization-activated cation current Ih by volatile anesthetic sevoflurane in the mouse striatum during postnatal development. (2017)
  • Author(s): 1.Sugasawa Y, Fukuda M, Ando N, Inoue R, Nakauchi S, Miura M, Nishimura K.
  • Journal Title: Neuroscience Research Volume: S0168-0102(17) Pages: 0402-9
  • DOI: 10.1016/j.neures.2017.09.009
  • Peer Reviewed
• [Journal Article] Leucine-rich α2-glycoprotein overexpression in the brain contributes to memory impairment (2017)
  • Author(s): 2.Akiba C, Nakajima M, Miyajima M, Ogino I, Miura M, Inoue R, Nakamura E, Kanai F, Tada N, Kunichika M, Yoshida M, Nishimura K, Kondo A, Sugano H, Arai H.
  • Journal Title: Neurobiology of Aging Volume: 60 Pages: 11-19
  • DOI: 10.1016/j.neurobiolaging.2017.08.014
  • Peer Reviewed / Open Access
• [Journal Article] Nicotinic acetylcholine receptor-mediated GABAergic inputs to cholinergic interneurons in the striosomes and the matrix compartments of the mouse striatum (2016)
  • Author(s): Inoue R, Suzuki T, Nishimura K, Miura M
  • Journal Title: Neuropharmacology. 2016 Volume: 105 Pages: 318-28
  • DOI: 10.1016/j.neuropharm.2016.01.029
  • Peer Reviewed
• [Presentation] 線条体機能領域におけるコリン作動性ニューロンへの興奮性入力調節の特異性 (2018)
  • Author(s): 井上律子、三浦正巳
  • Organizer: 首都大学東京バイオカンファレンス
• [Presentation] Activation of nicotinic acetylcholine receptors modulates excitatory inputs in the striatal cholinergic neurons (2018)
  • Author(s): Masami Miura, Ritsuko Inoue, Sakura Nakauchi
  • Organizer: 第41回日本神経科学大会
• [Presentation] A neurophysiological study of age-related motor impairment (2018)
  • Author(s): 井上律子、中内さくら、高橋眞由美、三浦正巳
  • Organizer: 第41回日本基礎老化学会大会
• [Presentation] Effect of exogenous coenzyme Q treatment on fEPSPs of the motor cortex of aged mice (2018)
  • Author(s): 井上律子、中内さくら、三浦正巳
  • Organizer: 第９５回日本生理学会大会
• [Presentation] Volatile anesthetic pretreatment alleviates the hypoxia-induced depolarization through ATP-sensitive potassium channels in the striatal medium spiny neurons of mice (2017)
  • Author(s): 福田征孝、安藤望、井上律子、中内さくら、三浦正巳、西村欣也
  • Organizer: 第４０回日本神経科学大会
• [Presentation] Protective effects of volatile anesthetic on depolarization by ischemia in the striatal neurons (2017)
  • Author(s): 三浦正巳、福田征孝、安藤望、井上律子、中内さくら、西村欣也
  • Organizer: 第４０回日本基礎老化学会大会
• [Presentation] 線条体におけるオピオイドの作用と局所神経回路 (2017)
  • Author(s): 三浦正巳
  • Organizer: 第１１回パーキンソン病・運動障害疾患コングレス
  • Invited
• [Presentation] Nicotinic and opioidergic modulation on inhibitory inputs to cholinergic interneurons in the striosomes and the matrix of the mouse striatum (2016)
  • Author(s): Inoue R, Miura M
  • Organizer: Dopamine 2016
  • Place of Presentation: ウィーン（オーストリア）
  • Year and Date: 2016-09-05
  • Int'l Joint Research
• [Presentation] コリン作動性ニューロンへのニコチン受容体を介したGABA性入力は線条体マトリックス優位である (2016)
  • Author(s): 井上律子、三浦正巳
  • Organizer: ３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-07-20
• [Presentation] An allosteric modulator of α4β2 nicotinic acetylcholine receptor potentiates GABAergic inputs to cholinergic interneurons in the mouse striatum (2016)
  • Author(s): Miura M, Inoue R
  • Organizer: CINP 2016
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] Differences of electrophysiological property between compartments of the mouse striatum in the methamphetamine-induced stereotypy (2016)
  • Author(s): 井上律子、三浦正巳
  • Organizer: 第４６回日本神経薬理学会年会
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2016-07-02
• [Presentation] ドーパミン受容体刺激による常同行動の神経基盤 (2016)
  • Author(s): 井上律子、三浦正巳
  • Organizer: 第３９回日本基礎老化学会大会
  • Place of Presentation: 伊勢原市民文化会館（神奈川県・伊勢原市）
  • Year and Date: 2016-05-27