Genetic manipulation of striosome neurons to study the pathomechanisms of neurodegenerative diseases in mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16494
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kyoto University
• Principal Investigator: Okunomiya Taro 京都大学, 医学研究科, 助教 (60868256)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 線条体 / ストリオソーム / μオピオイド受容体 / 運動制御 / DREADD / 病態モデル / 大脳基底核 / ジストニア

Outline of Final Research Achievements

The mammalian striatum is the major input nucleus of the basal ganglia and composed of two anatomical structures: the island-like striosome compartment and the surrounding matrix compartment. This compartmentalized structure has been suggested to be related to the motor control and its abnormalities, but the mechanisms remain to be elucidated. In this study, we chemogenetically manipulated striosome neuronal activity by injecting Cre-dependent virus vector into the striatum of the MOR-CreER mice, which allowed genetic manipulation of striosomal mu opioid receptor-expressing cells. Our results revealed a relationship between striatal neural function and locomotion in mice.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

マウス個体の線条体ストリオソーム神経細胞活動を人為的に制御できるマウスモデルを開発した。個体の片側線条体ストリオソームの神経活動操作による運動変化は、これまでの大脳基底核回路モデルでは説明できなかった。本研究の結果は、ストリオソーム神経細胞特異的な運動制御のメカニズムの一端を明らかにし、ジストニア等の運動異常症の発症機序の理解に役立つ可能性がある。