Identification of neural circuits underlying working memory impairments

• Project/Area Number: 17K16397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Dokkyo Medical University
• Principal Investigator: Arime Yosefu 獨協医科大学, 医学部, 講師 (80609404)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 統合失調症 / モデルマウス / ワーキングメモリー / 神経回路 / 前辺縁皮質 / 背内側線条体 / 動物モデル / In vivoカルシウムイメージング / in vivo カルシウムイメージング / 精神疾患 / 認知機能障害 / 神経科学

Outline of Final Research Achievements

Cognitive dysfunctions including working memory, which are considered to be a core symptom of schizophrenia, are resistant to the effects of antipsychotic medication.
In this study, we found an imbalance between excitatory and inhibitory synapses in layer 2–3 of the prelimbic cortex, which was previously identified as a responsible region for working memory impairments in mice chronically treated with phencyclidine (PCP). Our data suggested that the abnormalities of specific neural circuits in this region might form the neural basis of working memory impairments. We think we were able to collect foundational data on neural circuits that cause working memory impairments in a mouse model of schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

統合失調症の中核症状と考えられているワーキングメモリーなどの認知機能障害は、現存する抗精神病薬ではほとんど効果がない。また、その神経回路病態も不明である。本課題により得られた統合失調症のモデルマウスにおけるワーキングメモリー障害の原因神経回路に関する基盤的データは、神経回路活動の特異的な操作手法などを用いることによって認知機能障害の因果性の解明に迫ることを可能とし、将来的には統合失調症の認知機能障害を特異的に標的とした治療法の開発に寄与すると期待される。

Research Products

• [Journal Article] Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice (2017)
  • Author(s): Arime Y, Akiyama K
  • Journal Title: PLOS ONE Volume: 12 Issue: 12 Pages: e0189287-e0189287
  • DOI: 10.1371/journal.pone.0189287
  • Peer Reviewed / Open Access
• [Presentation] Examination of the findings suggesting Niemann-Pick disease type C in patients with schizophrenia. (2019)
  • Author(s): Fujii K, Maekawa M, Ozeki Y, Eto Y, Saito T, Shinozaki M, Arime Y, Nagashima T, Okayasu H, Ishii S, Shimoda K
  • Organizer: International Congress on Schizophrenia Research
  • Int'l Joint Research
• [Presentation] Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice. (2018)
  • Author(s): Arime Y, Akiyama K
  • Organizer: The Society for Neuroscience (SfN) 48th Annual Meeting
  • Int'l Joint Research
• [Presentation] Phencyclidine慢性投与マウスが示すワーキングメモリー障害の神経基盤の探索 (2018)
  • Author(s): 有銘預世布，秋山一文
  • Organizer: 第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
• [Presentation] 統合失調症と診断された症例を対象とした成人型ニーマンピック病C型を示唆する所見の検討 (2018)
  • Author(s): 藤井久彌子，前川正充，衞藤義勝，尾関祐二，齋藤尚大，有銘預世布，永島隆秀，岡安寛明，篠﨑隆央，秋山一文，下田和孝
  • Organizer: 第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会