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High-resolution spatiotemporal analysis of harmaline-induced tremor and inferior olive activity in living mice

Research Project

Project/Area Number 22K06478
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionOkinawa Institute of Science and Technology Graduate University

Principal Investigator

ウーシサーリ マルリカ・ヨエ  沖縄科学技術大学院大学, 神経活動リズムと運動遂行ユニット, 准教授 (30799656)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordscerebellum / inferior olive / tremor / motion capture / mouse / locomotion / harmaline / calcium imaging / in vivo / olivo-cerebellar system / essential tremor
Outline of Research at the Start

We will use a novel 3D mouse motion capture system combined with fluorescence-based activity monitoring of neurons to examine fundamental mechanisms underlying emergence of essential tremor.

Outline of Annual Research Achievements

In the past fiscal year, we successfully established and conducted the first large-scale motion capture (mocap) experiment with mice administered different doses of harmaline. The behavioral analysis was performed across four distinct tasks: open field exploration, treadmill running, balance beam traversal, and wheel-climbing. We not only captured the motion of the experimental animals but also implanted a GRIN-lens-based Inscopix imaging system to record neuronal activity in the cerebellar nuclei during these trials.
Our findings reveal a significant difference in neural activity between control and harmaline-treated animals. Specifically, while control animals exhibited a decrease in "neural noise" within the cerebellar nuclei during locomotion, harmaline-treated animals showed an increase in neural noise during similar activities. This divergence in neural activity suggests that harmaline disrupts the normal neural coordination associated with motor control, highlighting the cerebellar nuclei's role in motor disturbances induced by harmaline.
These results provide critical insights into the neural mechanisms underlying motor control and the impact of pharmacological agents on cerebellar function, which are pivotal for advancing our understanding of motor disorders.

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

We have had some difficulties in establishing imaging in strongly-tremoring animals but with advances in surgical methods (including novel combinations of dental cement and other components) we are making strides now. Furthermore, we are currently investigating novel analytical approaches for dealing with the very-high-dimensional behavioral and neuronal data. Methodology for constructing the motion-capture markers is improving, consistently providing higher-quality data.

Strategy for Future Research Activity

Recently starting to employ next-level analytical methodology, based on causality metrics from dynamical systems theory, to describe the body tremors in the context of neuronal activity. Part of the work is to be published as a component of a groundbreaking motion capture study in coming months.

Report

(2 results)
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (2 results)

All 2023

All Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Presentation] How minds move matter - on computation below cognition.2023

    • Author(s)
      Marylka Yoe Uusisaari
    • Organizer
      Tampere Gamification Group
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] “Information”: brain activity seen through the information landscape of animal.2023

    • Author(s)
      Marylka Yoe Uusisaari
    • Organizer
      Tohoku Creativity Forum
    • Related Report
      2023 Research-status Report
    • Invited

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Published: 2022-04-19   Modified: 2024-12-25  

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