The role of astrocytes in generation of locomotive rhythm in the lumbar spinal cord

• Project/Area Number: 26670676
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: National Hospital Organization Murayama Medical Center
• Principal Investigator: Mikami Yuji 独立行政法人国立病院機構村山医療センター(臨床研究部), 電気生理学研究室, 共同研究員 (20306749)
• Co-Investigator(Kenkyū-buntansha): 岡田 泰昌 独立行政法人国立病院機構村山医療センター(臨床研究部), 電気生理学研究室, 室長 (80160688)
• Research Collaborator: ONIMARU Hiroshi ; YAZAWA Itaru ; OKAZAKI Shuntaro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 歩行 / ロコモーション / 脊髄 / 腰髄 / カルシウムイメージング / グリア細胞 / アストロサイト / ニューロン / 歩行リズム / 摘出脊髄標本 / 歩行運動 / グリア伝達物質 / 運動神経

Outline of Final Research Achievements

Locomotion is one of the most important motor functions to maintain activity of daily life. Neural locomotor output is generated in the lumbar spinal cord, yet the cellular mechanism underlying the locomotor output generation is not elucidated. We have proposed a hypothesis that astrocytes are actively involved in generation of locomotive rhythm in the lumbar spinal cord. To examine this hypothesis, we conducted calcium imaging in the isolated lumbar spinal cord preparation of the neonatal rat. Fictive locomotion was induced with NMDA and 5-HT. Cellular activities in the L5 ventral horn were captured under a confocal microscope simultaneously with neural locomotive output from L5 ventral roots. Recorded cells were classified into neurons and astrocytes on the basis of calcium responses to low potassium in the presence of TTX. We found astrocytes that were synchronous with neural locomotive output. We suggest that astrocytes are functionally involved in generation of locomotive rhythm.

Research Products

• [Int'l Joint Research] Public Higher Med. Prof. School in Opole(Poland)
• [Journal Article] Respiratory toxicity of dimethyl sulfoxide (2016)
  • Author(s): Takeda K, Pokorski M, Sato Y, Oyamada Y, Okada Y.
  • Journal Title: Adv Exp Med Biol. Volume: 885 Pages: 89-96
  • DOI: 10.1007/5584_2015_187
  • ISBN: 9783319258515, 9783319258539
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of arundic acid, an astrocytic modulator, on the cerebral and respiratory functions in severe hypoxia (2015)
  • Author(s): Fukushi I, Takeda K, Yokota S, Hasebe Y, Sato Y, Pokorski M, Horiuchi J, Okada Y.
  • Journal Title: Respir Physiol Neurobiol. Volume: S1569-9048 Pages: 30084-7
  • DOI: 10.1016/j.resp.2015.11.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anatomical and functional pathways of rhythmogenic inspiratory premotor information flow originating in the pre-Bötzinger complex in the rat medulla (2014)
  • Author(s): Koshiya N, Oku Y, Yokota S, Oyamada Y, Yasui Y, Okada Y
  • Journal Title: Neuroscience Volume: 268 Pages: 194-211
  • DOI: 10.1016/j.neuroscience.2014.03.002
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Detecting causal influences among the locomotion-like cellular Ca and output neural activities in the lumbar spinal cord using state-space modeling (2017)
  • Author(s): Okazaki S, Mikami H, Yazawa I, Takeda K, Onimaru H, Okada Y
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28
• [Presentation] A novel model of respiratory rhythm generation: a mechanism by interaction of intrinsically oscillating astrocytes and neurons (2015)
  • Author(s): Okada Y, Oku Y, Sasaki T, Vivar C, Yokota S, Takeda K, Fukushi I, Yazawa I, Someya H, Tamura Y
  • Organizer: Neuroscience 2015, 45th Society for Neuroscience Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Astrocytes mediate short-term plasticity of breathing (2015)
  • Author(s): Okada Y, Takeda K, Someya H, Oku Y, Miwakeichi F, Ishiguro M, Tamura Y, Pokorski M
  • Organizer: Experimental Biology 2015
  • Place of Presentation: Boston, USA.
  • Year and Date: 2015-04-01
  • Int'l Joint Research
• [Presentation] Connectomics of the inspiratory center: Anatomical tract and propagation dynamics from the preBotzinger complex (2014)
  • Author(s): Okada Y, Oku Y, Yokota S, Oyamada Y, Yasui Y, Koshiya N
  • Organizer: Society for Neuroscience Meeting 2014 (Neuroscience2014)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] From chaotic recruitment of the pre-Botzinger complex (pre-BotC) to functional connectomics of inter-pre-BotC tract and pan-network premotor pathways (2014)
  • Author(s): Koshiya N, Oku Y, Okada Y, Smith JC
  • Organizer: The XIIIth Oxford Breathing Meeting, Respiratory and Cardiovascular
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2014-10-26 – 2014-10-31
  • Invited
• [Presentation] Active roles of meduIlary astrocytes in respiratory rhythm generation and plasticity (2014)
  • Author(s): Okada Y
  • Organizer: The XIIIth Oxford Breathing Meeting, Respiratory and Cardiovascular
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2014-10-26 – 2014-10-31
  • Invited