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Spinal neuronal mechanism for voiding reflex and its functional recovery by optogenetic control of the neuronal circuit

Research Project

Project/Area Number 20H04043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionHyogo Medical University

Principal Investigator

Furue Hidemasa  兵庫医科大学, 医学部, 教授 (20304884)

Co-Investigator(Kenkyū-buntansha) 神野 尚三  九州大学, 医学研究院, 教授 (10325524)
小林 憲太  生理学研究所, 行動・代謝分子解析センター, 准教授 (70315662)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2023: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywords可塑性 / 排尿 / 機能亢進 / 脊髄 / 神経回路 / 副交感節前ニューロン / DREADDs / 脊髄損傷 / 自律神経 / in vivoパッチラクプ / シナプス応答 / シナプス前性 / GABA / 介在ニューロン / 神経活動の人為的操作 / 副交感神経 / 節前ニューロン / 光遺伝学 / シナプス後性 / 副交感 / 神経機構 / 神経生理 / in vivoパッチクランプ法 / 機能回復
Outline of Research at the Start

排尿障害は神経変性疾患など中枢から末梢に至る神経因性の障害から下部尿路障害に至る様々なレベルで障害される為、その障害像を明らかにすることが重要である。そこで、排尿を指令する脊髄の中枢神経機構に着目し、未だ不明な正常排尿時の神経活動の実体や排尿脊髄回路の役割を、世界に先駆けて独自に開発した生理学的手法を用いた統合的研究により明らかにする。

Outline of Final Research Achievements

In this study, we investigated spinal neuronal mechanisms for voiding reflex by using newly developed in vivo electrophysiological recording methods, and further examined how spinal neuronal activities related to micturition were altered following spinal cord injury. Our electrophysiological analyses showed that preganglionic parasympathetic neurons were pre- and postsynaptically inhibited by GABAergic neurons located in laminae II-III. Spinal cord injury induced a functional loss of micturition reflex, but the neuronal activity of preganglionic parasympathetic neurons was still intact. An inhibition of spinal GABAergic neurons using Gi-DREADDs system resulted in a functional recovery of micturition reflex. The present spinal neuronal mechanism for voiding reflex may be useful for future studies of basic and clinical medical sciences.

Academic Significance and Societal Importance of the Research Achievements

排尿の中枢機構の詳細は、最近、橋の排尿中枢の神経機構が明らかにされているが、最終的な司令塔である脊髄副交感節前ニューロンの脊髄神経機構や、脊髄損傷後の神経機構の可塑的変化は未だ不明であった。本研究において脊髄機構の詳細を明らかにしたことは、神経生理学や神経科学の基礎医学の発展に寄与できる。また、臨床においても脊髄損傷後の神経因性膀胱では下部尿路機能の改善のみならず、脊髄をターゲットにした基礎医学的成果に基づいた新規治療法の開発に貢献できる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (36 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (18 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 18 results,  Open Access: 17 results) Presentation (12 results) (of which Invited: 8 results) Remarks (4 results)

  • [Int'l Joint Research] University of Bristol(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Alabama at Birmingham(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Anterior cingulate cross-hemispheric inhibition via the claustrum resolves painful sensory conflict2024

    • Author(s)
      Keisuke Koga, Kenta Kobayashi, Makoto Tsuda, Anthony E. Pickering, Hidemasa Furue
    • Journal Title

      Communications Biology

      Volume: 7(1):330. Issue: 1 Pages: 1-15

    • DOI

      10.1038/s42003-024-06008-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Optogenetic inhibition of spinal inhibitory neurons facilitates mechanical responses of spinal wide dynamic range neurons and causes mechanical hypersensitivity2024

    • Author(s)
      Yuka Fujiwara, Keisuke Koga, Nozomu H Nakamura, Keishi Maruo, Toshiya Tachibana, Hidemasa Furue
    • Journal Title

      Neuropharmacology

      Volume: 242:109763. Pages: 1-9

    • DOI

      10.1016/j.neuropharm.2023.109763

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hippocampal ensemble dynamics and memory performance are modulated by respiration during encoding2023

    • Author(s)
      Nozomu H. Nakamura, Hidemasa Furue, Kenta Kobayashi, Yoshitaka Oku
    • Journal Title

      nature communications

      Volume: 14(1):4391. Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41467-023-40139-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An electrophysiological method for evaluation of topical antipruritic drugs on itch-related neuronal activities in the spinal cord in hairless mice2023

    • Author(s)
      Yuhki Ueda, Daisuke Uta, Hidemasa Furue, Yoshitaka Ohtubo
    • Journal Title

      European Journal of Pharmacology

      Volume: 952:175798. Pages: 1-11

    • DOI

      10.1016/j.ejphar.2023.175798

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Voltage-gated calcium channel subunit α2δ-1 in spinal dorsal horn neurons contributes to aberrant excitatory synaptic transmission and mechanical hypersensitivity after peripheral nerve injury2023

    • Author(s)
      Koga Keisuke、Kobayashi Kenta、Tsuda Makoto、Kubota Kazufumi、Kitano Yutaka、Furue Hidemasa
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 16 Pages: 1-13

    • DOI

      10.3389/fnmol.2023.1099925

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Properties of Nav1.8ChR2-positive and Nav1.8ChR2-negative afferent mechanoreceptors in the hindpaw glabrous skin of mice2023

    • Author(s)
      Yamada Akihiro、Yamada Ayaka I.、Ling Jennifer、Furue Hidemasa、Luo Wenqin、Gu Jianguo G.
    • Journal Title

      Molecular Brain

      Volume: 16 (1):27 Issue: 1 Pages: 1-15

    • DOI

      10.1186/s13041-023-01015-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25?Nrf2 pathway2023

    • Author(s)
      Tanaka Tatsuhide、Okuda Hiroaki、Isonishi Ayami、Terada Yuki、Kitabatake Masahiro、Shinjo Takeaki、Nishimura Kazuya、Takemura Shoko、Furue Hidemasa、Ito Toshihiro、Tatsumi Kouko、Wanaka Akio
    • Journal Title

      Nature Immunology

      Volume: 24 Issue: 3 Pages: 439-451

    • DOI

      10.1038/s41590-022-01418-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of acetaminophen on neuronal activity in the mouse locus coeruleus2022

    • Author(s)
      Seki Iwao、Nakamura Ayumi、Koga Keisuke、Aono Hiroyuki、Furue Hidemasa
    • Journal Title

      PAIN RESEARCH

      Volume: 37 Issue: 1 Pages: 16-25

    • DOI

      10.11154/pain.37.16

    • ISSN
      0915-8588, 2187-4697
    • Year and Date
      2022-03-30
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural and functional properties of spinal dorsal horn neurons after peripheral nerve injury change overtime via astrocyte activation2022

    • Author(s)
      Kurabe Miyuki、Sasaki Mika、Furutani Kenta、Furue Hidemasa、Kamiya Yoshinori、Baba Hiroshi
    • Journal Title

      iScience

      Volume: 25 Issue: 12 Pages: 105555-105555

    • DOI

      10.1016/j.isci.2022.105555

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angular Tuning Properties of Low Threshold Mechanoreceptors in Isolated Rat Whisker Hair Follicles2022

    • Author(s)
      Yamada Akihiro、Furue Hidemasa、Gu Jianguo G.
    • Journal Title

      eneuro

      Volume: 9(6) ENEURO.0175~22.2022 Issue: 6 Pages: 1-14

    • DOI

      10.1523/eneuro.0175-22.2022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Excess intracellular ATP causes neuropathic pain following spinal cord injury2022

    • Author(s)
      Nobuhiko Nakajima , Yuichiro Ohnishi , Masamichi Yamamoto , Daiki Setoyama , Hirohiko Imai , Tomofumi Takenaka , Mari Matsumoto , Koichi Hosomi , Yoichi Saitoh , Hidemasa Furue , Haruhiko Kishima
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 79 Issue: 9 Pages: 483-483

    • DOI

      10.1007/s00018-022-04510-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tmem45b is essential for inflammation- and tissue injury?induced mechanical pain hypersensitivity2022

    • Author(s)
      Tanioku Tadashi、Nishibata Masayuki、Tokinaga Yasuyuki、Konno Kohtaro、Watanabe Masahiko、Hemmi Hiroaki、Fukuda-Ohta Yuri、Kaisho Tsuneyasu、Furue Hidemasa、Kawamata Tomoyuki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 45 Pages: 119-119

    • DOI

      10.1073/pnas.2121989119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脊髄副交感節前ニューロンからのin vivo電気生理学的記録法2022

    • Author(s)
      古江秀昌、中村喜隆、中村亜由美、古賀啓祐
    • Journal Title

      自律神経

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anesthesia and surgery induce a functional decrease in excitatory synaptic transmission in prefrontal cortex neurons, and intraoperative administration of dexmedetomidine does not elicit the synaptic dysfunction2021

    • Author(s)
      Matsumoto Yu、Fujino Yuji、Furue Hidemasa
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 572 Pages: 27-34

    • DOI

      10.1016/j.bbrc.2021.07.065

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior2021

    • Author(s)
      Tashima Ryoichi、Koga Keisuke、Yoshikawa Yu、Sekine Misuzu、Watanabe Moeka、Tozaki-Saitoh Hidetoshi、Furue Hidemasa、Yasaka Toshiharu、Tsuda Makoto
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 3

    • DOI

      10.1073/pnas.2021220118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-nociceptive and anxiolytic effects of systemic flupirtine and its direct inhibitory actions on in vivo neuronal mechanical sensory responses in the adult rat anterior cingulate cortex.2020

    • Author(s)
      Matsumoto Y, Fujino Y, Furue H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 531(4) Issue: 4 Pages: 528-534

    • DOI

      10.1016/j.bbrc.2020.07.129

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of cannabinoid type 1 receptor in fasting-induced analgesia.2020

    • Author(s)
      Lee JY, Lee GJ, Nakamura A, Lee PR, Kim Y, Won CH, Furue H, Oh SB.
    • Journal Title

      Mol Pain

      Volume: 16 Pages: 1-10

    • DOI

      10.1177/1744806920969476

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons2020

    • Author(s)
      Uta Daisuke、Koga Kohei、Furue Hidemasa、Imoto Keiji、Yoshimura Megumu
    • Journal Title

      Anesthesiology

      Volume: 134 Issue: 1 Pages: 88-102

    • DOI

      10.1097/aln.0000000000003596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 睡眠障害が疼痛行動や前帯状皮質神経活動に与える影響2024

    • Author(s)
      中野 康佑
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 睡眠障害や疼痛に対する前帯状回皮質神経活動の可塑的変化.2023

    • Author(s)
      古江秀昌
    • Organizer
      第45回日本疼痛学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 光遺伝学的脊髄GABAニューロンの脱抑制による異常痛覚応答とa20-lリガンドによる鎮痛効果.2023

    • Author(s)
      藤原優香
    • Organizer
      第45回日本疼痛学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 痛覚の中枢性制御機構と神経障害性疼痛薬の作用機構.2023

    • Author(s)
      古江秀昌
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 痛みの基礎研究 最近の研究について-α2δサブユニットを標的とした鎮痛・神経機構-.2023

    • Author(s)
      古江秀昌
    • Organizer
      日本ペインクリニック学会 第57回学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 脳内ストレスにおける疼痛の情動神経機構2022

    • Author(s)
      古江 秀昌
    • Organizer
      第18回日本疲労学会総会・学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Action of baclofen on micturition and parasympathetic preganglionic neurons in the sacral spinal cord2022

    • Author(s)
      Yoshitaka Nakamura, Ayumi Nakamura, Keisuke Koga, Hidemasa Furue
    • Organizer
      第99回日本生理学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生理学的視点からの排尿のin vivo脊髄シナプス機構2021

    • Author(s)
      古江秀昌
    • Organizer
      第74回日本自律神経学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 光・薬理遺伝学的手法とin vivoパッチクランプ法を組み合わせた疼痛発現およびその調節機構の解析2021

    • Author(s)
      古江 秀昌
    • Organizer
      第43回日本疼痛学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 痛みや痒み神経のシナプス応答リアルタイム記録と中枢機構の解析2021

    • Author(s)
      古江秀昌
    • Organizer
      「感覚研究コンソーシアム」 第2回ピッチイベント(オンライン)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 副交感節前ニューロンに誘起される感覚シナプス応答と脊髄排尿調節機構2021

    • Author(s)
      古江秀昌
    • 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
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 大脳辺縁系における疼痛応答とその調節機構.2020

    • Author(s)
      古江秀昌
    • Organizer
      第42回日本疼痛学会. オンライン開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 兵庫医科大学医学部生理学神経生理部門ホームページ

    • URL

      https://www.hyo-med.ac.jp/department/neurophysiol/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 兵庫医科大学 生理学神経生理部門ホームページ

    • URL

      https://www.hyo-med.ac.jp/department/neurophysiol/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 兵庫医科大学生理学神経生理部門ホームページ

    • URL

      https://www.hyo-med.ac.jp/department/neurophysiol/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 兵庫医科大学 生理学 神経生理部門ホームページ

    • URL

      https://www.hyo-med.ac.jp/department/neurophysiol/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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