Chemogenetic manipulation reveals pathway-specific functions of the cerebellar efferent of macaque monkeys

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: ISHIDA Hiroaki 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (70728162)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 化学遺伝学 / 小脳遠心路 / PETイメージング / マカクザル / 運動障害 / 遺伝子導入 / アデノ随伴ウイルス / ムシモル

Outline of Final Research Achievements

The purpose of this study was to use chemogenetic methods to manipulate projection pathways in the cerebellum of monkeys to clarify the functional role of the pathways. AAV vectors expressing DREADD were injected into the dentate nucleus of the monkey cerebellum and expression levels were evaluated using positron emission tomography. After sufficient expression was confirmed in the monkey cerebellum, the projection pathway was reversibly blocked and changes in monkey reaching movements, muscle activity, and neural activity in each brain region were recorded. The analysis did not show an effect of the manipulation by DREADD. It is possible that temporary inhibition of unilateral cerebellar projection pathways does not cause changes due to the learning and adaptive ability of the cerebellum.

Free Research Field

システム神経生理学

Academic Significance and Societal Importance of the Research Achievements

霊長類の脳を用いた遺伝子導入技術の確立を目指した。サルを用いて小脳投射経路の操作が実現することによって因果関係に基づいた神経経路機能が明らかになり、ヒト運動失調の病態理解や新しいリハビリテーション法の開発が促進される。