Analysis of GABA synaptic modulation on neuronal activity and the remodeling of medial lemniscal fibers after the peripheral nerve injury in the somatosensory thalamus: using lentivirus vector method

• Project/Area Number: 24790580
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: NAGUMO Yasuyuki 東京女子医科大学, 医学部, 助教 (00459661)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脳・神経 / 神経科学 / 体性感覚視床 / 神経損傷 / GABA / 内側毛帯線維 / 神経回路再改編

Outline of Final Research Achievements

We previously reported that cut of the infraorbital nerve (IONC) recruits additional excitatory medial lemniscal fibers onto somatosensory thalamic neurons (VPM neurons) within a week. On the other hand, it is also reported that peripheral nerve injury induces remodeling in the central nervous system through functional changes of inhibitory GABA system. However, it remains unclear whether the remodeling of lemniscal fibers onto a VPM neuron after the IONC is mediated by postoperative changes in inhibitory GABA currents. Here we report that the IONC markedly enhanced the amplitude of tonic GABA currents onto a VPM neuron that had multiple lemniscal fibers by the IONC. Moreover, we found that lack of tonic GABA currents by lentivirus vector prevented the remodeling of lemniscal fibers onto a VPM neuron after the IONC. These results indicate that the remodeling of lemniscal fibers onto a VPM neuron after the IONC is mediated by enhanced tonic GABA inhibition by the IONC.

Research Products

• [Journal Article] FFA1-selective agonistic 1570..1583 activity based on docking simulation using FFA1 and GPR120 homology models (2013)
  • Author(s): Masato Takeuchi
  • Journal Title: British Journal of Pharmacology Volume: 168 Issue: 7 Pages: 1570-1583
  • DOI: 10.1111/j.1476-5381.2012.02052.x
  • Peer Reviewed
• [Presentation] Enhanced tonic GABA currents after peripheral nerve injury contribute to inhibition of neuronal activity and subsequent remodeling of medial lemniscal fibers in the somatosensory thalamus (2015)
  • Author(s): Nagumo Y, Takeuchi Y, Osaki H, Miyata M
  • Organizer: 第 120 回日本解剖学会総会 第 92 回日本生理学会大会 合同大会
  • Place of Presentation: 神戸: 神戸国際会議場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Role of extrasynaptic GABAA receptor on the remodeling of medial lemniscal fibers in the somatosensory thalamus by peripheral nerve injury (2014)
  • Author(s): Nagumo Y, Miyata M
  • Organizer: 第 37 回 日本神経科学大会 (Neuroscience 2014)
  • Place of Presentation: 横浜: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Phasic-GABA current in thalamic relay neurons is reduced by peripheral nerve injury, whereas tonic-GABA current is increased (2013)
  • Author(s): Nagumo Y, Miyata M
  • Organizer: 第 36 会日本神経科学会年会 (Neuro 2013)
  • Place of Presentation: 京都: 国立京都国際会館
• [Presentation] Contrary changes of phasic- and tonic-inhibition onto thalamic relay neurons in mice with infraorbital nerve cut (2013)
  • Author(s): Nagumo Y, Miyata M.
  • Organizer: 第 90 回日本生理学会大会
  • Place of Presentation: 東京: タワーホール船掘
• [Book] トワイクロス先生のがん緩和ケア処方薬 薬効・薬理と薬の使い方 (2013)
  • Author(s): 監訳: 武田文和、鈴木 勉、共著パート翻訳: 南雲康行
  • Total Pages: 752
  • Publisher: 医学書院