Local excitatory / inhibitory neuronal circuit in prefrontal cortex developed by social experience can be a target for treatment?

• Project/Area Number: 16K10221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nara Medical University
• Principal Investigator: Yoshino Hiroki 奈良県立医科大学, 医学部, 准教授 (10347560)
• Research Collaborator: MAKINODAN manabu 奈良県立医科大学, 精神医学教室, 講師
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 社会的経験 / 前頭葉 / 興奮性 / 抑制性 / 錐体細胞 / 介在ニューロン / 社会経験 / 発達 / 前頭前野 / 隔離 / 神経発達 / 精神疾患 / 神経科学 / 電気生理

Outline of Final Research Achievements

Based on the previous report that lack of social experience impair development of human prefrontal cortex, I started the project to examine whether isolate-rearing affect pyramidal cell (excitatory) and interneuron (inhibitory) in mouse medial prefrontal cortex. In my previous study, it was found that social isolation lowered the excitability of specific pyramidal cell in mouse medial prefrotnal cortex. In this study, social isolation also increased inhibitory synaptic inputs onto the specific pyramidal cell, and increased the excitability of fast-spiking interneuron which is main candidate of the source of inhibitory inputs onto the pyramidal cell. Furthermore social isolation decreased excitatory synaptic inputs onto fast-spiking interneuron.

Academic Significance and Societal Importance of the Research Achievements

ヒトの高度な脳機能を発揮するには、神経回路が適正な興奮性と抑制性のバランスを保つ必要がある。一方で、ヒトらしい高度な脳機能を支える重要な脳領域の前頭葉の発達には、発達期の社会的経験が必要である。そこで、隔離飼育され社会的経験を剥奪されたマウスの前頭葉において、神経回路の興奮性/抑制性バランスにどのような変化が見られるかを調べた。結果、興奮性を担う錐体細胞の活動は低下しており、抑制性を担う介在神経細胞の活動が増加して興奮性/抑制性バランスが崩れていることがわかった。ヒトの発達期の乏しい社会的経験は、前頭葉神経回路の興奮性/抑制性のアンバランスによる脳の機能低下につながる可能性が考えられた。

Research Products

• [Journal Article] Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex. (2017)
  • Author(s): Yamamuro K, Yoshino H, Ogawa Y, Makinodan M, Toritsuka M, Yamashita M, Corfas G, Kishimoto T.
  • Journal Title: Cereb Cortex. Volume: 1-13 Issue: 3 Pages: 998-1010
  • DOI: 10.1093/cercor/bhx010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Social isolation during developmental critical window affects inhibitory neuronal circuit in mouse mPFC (2019)
  • Author(s): Hiroki Yoshino, Kazuhiko Yamamuro, Yoichi Ogawa, Manabu Makinodan, Yasuhiko Saito, Toshifumi Kishimoto
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies congress, Kobe, 2019
  • Int'l Joint Research
• [Presentation] Social isolation during the critical period reduces synaptic and intrinsic excitability of a subtype of pyramidal cell in mouse prefrontal cortex (2017)
  • Author(s): H. YOSHINO, K. YAMAMURO, Y. OGAWA, M. MAKINODAN, M. TORITSUKA, K. OKAMURA, Y. NISHIHATA, Y. YAMAGUCHI, S. KIMOTO, M. YAMASHITA, G. CORFAS, T. KISHIMOTO
  • Organizer: Society for Neuroscience 47th Annual Meeting
  • Int'l Joint Research
• [Presentation] 社会的隔離はマウス前頭前野の特定の錐体細胞の興奮性を低下させる (2017)
  • Author(s): 芳野浩樹、山室和彦、小川陽一、鳥塚通弘、岡村和哉、西畑陽介、 山口泰成、紀本創兵、山下勝幸、Corfas Gabriel、牧之段学、岸本年史
  • Organizer: 第39回日本生物学的精神医学会 第47回日本神経精神薬理学会 合同年会
• [Presentation] Lack of Social Experience Disrupts E/I Balance in Medial Prefrontal Cortex (2016)
  • Author(s): Hiroki Yoshino
  • Organizer: Regional Latin American Congress of The World Federation of Societies of Biological Psychiatry 2016
  • Place of Presentation: Lima, Peru
  • Year and Date: 2016-11-25
  • Int'l Joint Research