Research on neural circuit in decision-making by using cell- and projection-specific manner of chemogenetics and computational approach

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H03303
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Nagoya University
• Principal Investigator: Mizoguchi Hiroyuki 名古屋大学, 環境医学研究所, 講師 (70402568)
• Research Collaborator: YAMANAKA akihiro ; OHIRA hideki ; KATAHIRA kentaro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 意思決定 / DREADD / 島皮質 / 神経回路 / 精神疾患

Outline of Final Research Achievements

Decision-making is a key activity process that influences many aspects of daily living and both mental and physical health. In general, healthy participants reveal rational choice, but patients with neuropsychiatric disorders reveal irrational and risky choice in decision-making. A better understanding of the mechanisms underlying altered decision-making would provide insights into potential therapeutic approaches for these diseases. However, the neural pathway and substrates underlying these deficits are particularly unknown. In this research, we demonstrated that insular cortex, nucleus accumbens, and striatum are key regions for risky decision-making. Our findings suggest that disinhibition of glutamatergic neurons as well as dysfunction of GABAergic interneurons in the insular cortex, plays a role in altered decision-making. Further research on the insular-striatal pathway would be necessary to understand the mechanisms underlying impaired decision-making.

Free Research Field

神経精神薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により意思決定に関わる神経回路および分子機構を解明することができ、高次脳機能の根本的理解が進み、神経精神薬理学の分野に留まらず、脳科学の発展に大きく貢献できた。また、社会的問題として取り上げられているゲーム依存やギャンブル依存といった意思決定の異常を伴う多くの神経精神疾患の病態の解明と治療薬の開発につながる成果である。臨床研究と基礎研究をつなぐトランスレーショナルテスト・動物モデルとして、今後の創薬研究において極めて有用な研究成果である。