Neuro recovery and control for decision making

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19430
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: Kyoto University
• Principal Investigator: Sasaki Ryo 京都大学, 医学研究科, 助教 (70817931)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 意思決定 / マカクサル / オプトジェネティクス / 腹側被蓋野

Outline of Final Research Achievements

This study attempted to elucidate the brain mechanisms underlying the risk-dependency of decision making by using macaque monkeys trained a high risk-high return (HH) versus low risk-low return (LL) choice task. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of area vlPFC during the monkeys’ decision period facilitated a preference for HH. In contrast, activation of the pathway from VTA to the dorsal aspect of area dlPFC facilitated a preference for LL. Besides, the effects of successive stimulation of each pathway accumulated over time, and even when not stimulated, the monkeys shifted further to the HH/LL-preferring mode, with a marked enhancement or inhibition of the HH-preferring cue-related responses in area vlPFC/dlPFC. These results suggest that VTA inputs to area vlPFC/dlPFC balance the choices between HH and LL in both the short and long term.

Free Research Field

神経生物

Academic Significance and Societal Importance of the Research Achievements

精神障害の根本原理の解明と治療法の開発が現代医療の最大の課題の一つともいえる中、本研究では光遺伝学技術を用い、巨大脳を有するマカクサルでのオプトジェネティクスを成し遂げた。神経回路の起始停止を定め直接的に活性化及び不活性化を施すことで、意思決定機能の細部に正確かつ直接的に作用した。光遺伝学的手法による神経路選択的な操作を用いた神経回路レベルでの長期介入から、リスク依存的意思決定様式の形成過程を示す脳内機構の解明を試みた研究は過去に見られない。ヒトの意思決定様式の形成過程を示す脳内機構の解明と、精神神経疾患の治療戦略モデル提唱に向けた実証的な結果が得られたといえる。