The fundamental relationship between the density of astrocytes and synaptic transmission

• Project/Area Number: 17K08328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Fukuoka University
• Principal Investigator: Katsurabayashi Shutaro 福岡大学, 薬学部, 准教授 (50435145)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: シナプス伝達 / グリア細胞 / アストロサイト / サイレントシナプス / 細胞情報伝達学

Outline of Final Research Achievements

The astrocyte, a primary glial cell type, is involved in the formation and maturation of synapses, and thus contributes to sustainable synaptic transmission between neurons. Given that the animals in the higher phylogenetic tree have brains with a higher density of glial cells for neurons, there is a possibility that the relative astrocytic density directly influences synaptic transmission. Here we addressed it by using a primary culture preparation and patch-clamp electrophysiology. Neurons with a higher astrocytic density showed a higher excitatory synaptic transmission than that of neurons with a lower astrocytic density. The number of morphologically identified glutamatergic synapses was unchanged, but the proportion of functional ones was increased, indicating a lower ratio of presynaptically silent synapses. Taken together, the higher astrocytic density enhanced excitatory synaptic transmission by increasing the fraction of functional synapses through presynaptic un-silencing.

Academic Significance and Societal Importance of the Research Achievements

脳高次機能を有する高等動物ほど、脳内のグリア細胞の数が多いといわれています。その多数を占めるアストロサイトが欠如すると、神経回路の架け橋である『シナプス』の数は激減し、伝達物質放出機能も低下します。研究代表者はこれまでに、アストロサイトの液性因子は重要であるが、アストロサイトの占有面積とシナプス機能には相関関係はないことを報告しました。
この成果を更に発展させるため、本研究ではアストロサイトの“密度”に着目し、アストロサイトとニューロンの混成比の違いによるシナプス機能（情報伝達）とシナプス形態（形成秩序）を解析し、アストロサイト密度と高次機能の相関関係を明らかにしました。

Research Products

• [Int'l Joint Research] University of Iowa(米国)
• [Int'l Joint Research] University of Iowa(米国)
• [Journal Article] Effect of Yokukansan and Yokukansankachimpihange on Aggressive Behavior, 5-HT Receptors and Arginine Vasopressin Expression in Social Isolation-Reared Mice (2019)
  • Author(s): Iba H, Watanabe T, Matsuzawa K, Saimiya M, Tanaka M, Moriyama H, Kubota K, Katsurabayashi S, Iwasaki K
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 42 Issue: 12 Pages: 2009-2015
  • DOI: 10.1248/bpb.b19-00499
  • NAID: 130007754660
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2019-12-01
  • Peer Reviewed
• [Journal Article] Effect of Lactobacillus paracasei A221‐fermented ginseng on impaired spatial memory in a rat model with cerebral ischemia and β‐amyloid injection (2019)
  • Author(s): Masaki Nagao, Satoshi Yamano, Naoki Imagawa, Kentaro Igami, Toshitsugu Miyazaki, Hisatomi Ito, Takuya Watanabe, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki
  • Journal Title: Traditional & Kampo Medicine Volume: 6 Issue: 2 Pages: 96-104
  • DOI: 10.1002/tkm2.1220
  • Peer Reviewed
• [Journal Article] Hippocampal neurons in direct contact with astrocytes exposed to amyloid β25-35 exhibit reduced excitatory synaptic transmission (2019)
  • Author(s): Kohei Oyabu, Hiroki Kiyota, Kaori Kubota, Takuya Watanabe, Shutaro Katsurabayashi, Katsunori Iwasaki
  • Journal Title: IBRO Reports Volume: 7 Pages: 34-41
  • DOI: 10.1016/j.ibror.2019.07.1719
  • Peer Reviewed / Open Access
• [Journal Article] 神経突起萎縮やシナプス減少を呈する新規神経変性モデル培養標本の構築 (2019)
  • Author(s): 窪田香織、桂林秀太郎
  • Journal Title: Research Volume: 24 Pages: 87-89
• [Journal Article] Pioneer Factor NeuroD1 Rearranges Transcriptional and Epigenetic Profiles to Execute Microglia-Neuron Conversion. (2019)
  • Author(s): Matsuda T, Irie T, Katsurabayashi S, Hayashi Y, Nagai T, Hamazaki N, Adefuin AMD, Miura F, Ito T, Kimura H, Shirahige K, Takeda T, Iwasaki K, Imamura T, Nakashima K.
  • Journal Title: Neuron Volume: 101 (3) Issue: 3 Pages: 472-485
  • DOI: 10.1016/j.neuron.2018.12.010
  • Peer Reviewed / Open Access
• [Journal Article] Dependence and Homeostasis of Membrane Impedance on Cell Morphology in Cultured Hippocampal Neurons. (2018)
  • Author(s): Matsumura R, Yamamoto H, Hayakawa T, Katsurabayashi S, Niwano M, Hirano-Iwata A.
  • Journal Title: Scientific Reports Volume: 8 (1) Issue: 1 Pages: 9905-9905
  • DOI: 10.1038/s41598-018-28232-0
  • Peer Reviewed / Open Access
• [Journal Article] Astrocytes with previous chronic exposure to amyloid beta-peptide fragment 1–40 suppress excitatory synaptic transmission. (2017)
  • Author(s): Kawano H, Oyabu K, Yamamoto H, Eto K, Adaniya Y, Kubota K, Watanabe T, Hirano-Iwata A, Nabekura J, Katsurabayasi S, Iwasaki K.
  • Journal Title: J Neurochemistry Volume: 143 Issue: 6 Pages: 624-634
  • DOI: 10.1111/jnc.14247
  • Peer Reviewed
• [Journal Article] The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB. (2017)
  • Author(s): Kubota K, Fukue H, Sato H, Hashimoto K, Fujikane A, Moriyama H, Watanabe T, Katsurabayashi S, Kainuma M, Iwasaki K.
  • Journal Title: Front Pharmacol. Volume: 21 Pages: 850-850
  • DOI: 10.3389/fphar.2017.00850
  • Peer Reviewed / Open Access
• [Presentation] Glial assembly for regenerative medicine and brain transplant (2020)
  • Author(s): Shutaro Katsurabayashi, Kohei Oyabu, Kotomi Takeda, Kaori Kubota, Takuya Watanabe, Katsunori Iwasaki
  • Organizer: 2nd Mini-Symposium on The Blood-Brain Barrier from Basic to Clinical Research
  • Int'l Joint Research / Invited
• [Presentation] 構成論的に神経ネットワークを作る～人工脳を作るための細胞レシピ～ (2019)
  • Author(s): 桂林 秀太郎
  • Organizer: 第20回ブレインサイエンス研究会
• [Presentation] Excitatory synaptic transmission in hippocampal neurons is reduced by direct contact with astrocytes exposed to amyloid β25-35 (2019)
  • Author(s): Oyabu K, Kiyota H, Kubota K, Watanabe T, Katsurabayashi S, Iwasaki K
  • Organizer: The 6th Congress of Asian College of Neuropsychopharmacology
  • Int'l Joint Research
• [Presentation] The direct contact of astrocytes to neuron is critical for lowering excitatory synaptic transmission after the exposure of amyloid β-protein 25-35 onto astrocytes (2019)
  • Author(s): Oyabu K, Kiyota H, Kubota K, Watanabe T, Katsurabayashi S, Iwasaki K
  • Organizer: Society for Neuroscience meeting
  • Int'l Joint Research
• [Presentation] Excitatory synaptic transmission is modulated by the density of surrounding astrocytes (2019)
  • Author(s): Kohei Oyabu, Shutaro Katsurabayashi, Katsunori Iwasaki
  • Organizer: The 7th RIEC International Symposium on Brain Functions and Brain Computer
  • Int'l Joint Research
• [Presentation] Excitatory synaptic transmission is reduced by astrocytes previously exposed to amyloid β peptide fragment 1-40 (2019)
  • Author(s): Oyabu K, Kawano H, Yamamoto H, Eto K, Adaniya Y, Kubota K, Watanabe T, Hirano-Iwata A, Nabekura J, Katsurabayashi S, Iwasaki K
  • Organizer: The 9th Federation of Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research
• [Presentation] アストロサイトと単一ニューンの比率変化が及ぼすシナプス伝達変化 (2018)
  • Author(s): 大藪康平、武田琴水、渡辺拓也、窪田香織、桂林秀太郎、岩崎克典
  • Organizer: 第19回ブレインサイエンス研究会
• [Presentation] ニューロン／アストロサイト混成比とシナプス伝達 (2018)
  • Author(s): 桂林 秀太郎、大藪 康平、武田 琴水、渡辺 拓也、窪田 香織、岩崎 克典
  • Organizer: 第27回神経行動薬理若手研究者の集い
• [Presentation] 人工脳を作るための細胞レシピ～構成論的に神経ネットワークを作る試み～ (2018)
  • Author(s): 桂林 秀太郎
  • Organizer: 福岡大学 学際シンポジウム
  • Invited