In vivo tracing of single neuron activity of primary somatosensory cortex in mice pain models

• Project/Area Number: 18K16482
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kobe University
• Principal Investigator: OKADA TAKUYA 神戸大学, 医学部附属病院, 非常勤医師 (70792935)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 生体イメージング / 疼痛 / 大脳皮質体性感覚野 / 化学遺伝学的手法 / 生体カルシウムイメージング / 2光子顕微鏡 / 第一次体性感覚野 / 術後痛 / 炎症性痛 / 大脳皮質第一次体性感覚野 / 化学遺伝学 / 神経細胞活動

Outline of Final Research Achievements

In this research, to visualize neuronal activity, the adeno associated virus encoding the synapsin promoter driven calcium indicator protein GCaMP6f was expressed in layer Ⅱ/Ⅲ excitatory neurons of primary somatosensory cortex（S1）, we investigated the activity pattern of S1 neurons by using in vivo two-photon calcium imaging. We analyzed time dependent changes of neuronal activity and synchronization of neuronal activity during acute phase of pain in mice models of pain. As a results, the paw withdrawal threshold was significantly decreased in the affected hind paw of both models in acute pain phase. Therefore, the integral value of Ca2+ traces and the correlational activity among GCaMP6f-expressing excitatory neurons increased in both models in acute pain phase. Furthermore, by using chemogenetic method, we succeeded to enhance or inhibit neuronal activity of S1 neurons in vivo. We found the threshold of pain significantly changed by artificial control of S1 neuronal activity.

Academic Significance and Societal Importance of the Research Achievements

近年、慢性疼痛の病態形成において大脳皮質第一次体性感覚野 (S1) の神経活動変化の重要性が示唆されるようになってきた。しかし、生体内で同一神経細胞活動を経時的に観察し、疼痛形成のメカニズムを検討した研究は少なかった。本研究によりS1の個々の神経細胞活動と疼痛閾値には関連があり、疼痛形成および維持においてS1の個々の神経活動変化およびそれらの相関性が重要である可能性が示唆された。本研究の成果から、疼痛急性期の治療において、S1の神経細胞活動を抑制することを焦点とした新規治療法の開発につながることが期待できる。

Research Products

• [Presentation] In vivo tracing of single neuron activity of primary somatosensory cortex in mice pain models (2019)
  • Author(s): Okada Takuya, Nomura Yuki, Tachibana Yoshihisa, Obata Norihiko, Wake Hiroaki, Mizobuchi Satoshi.
  • Organizer: American Society of Anesthesiologist Annual Meeting
  • Int'l Joint Research
• [Presentation] In vivo Ca2+ imaging of somatosensory cortex in postoperative and inflammatory pain models of mice (2019)
  • Author(s): Okada Takuya, Tachibana Yoshihisa, Nomura Yuki, Obata Norihiko, Mizobuchi Satoshi, Wake Hiroaki.
  • Organizer: The 9th Federation of Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research
• [Presentation] 生体カルシウムイメージングによる大脳皮質第一次体性感覚野における同一 神経細胞活動の変化が疼痛閾値に与える影響の検討 (2019)
  • Author(s): 岡田卓也, 野村有紀, 小幡典彦, 橘吉寿, 和氣弘明, 溝渕知司
  • Organizer: 日本麻酔科学会
• [Presentation] 大脳皮質感覚野の生体イメージングによる疼痛発症機構解明へのアプローチ (2018)
  • Author(s): 岡田 卓也、橘 吉寿、野村 有紀、小幡 典彦、溝渕 知司、和氣 弘明
  • Organizer: 第111回近畿生理学談話会
• [Presentation] In vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory pain (2018)
  • Author(s): Takuya Okada, Yoshihisa Tachibana, Yuki Nomura, Norihiko Obata, Satoshi Mizobuchi, Hiroaki Wake
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] In vivo Ca2+ imaging of primary somatosensory cortex in a mouse model of postoperative pain (2018)
  • Author(s): 岡田 卓也、橘 吉寿、野村 有紀、小幡 典彦、溝渕 知司、和氣 弘明
  • Organizer: 第41回日本神経科学大会