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Movement-related increases in subthalamic activity optimize locomotion.

Joshua W Callahan, Juan Carlos Morales, Jeremy F Atherton

    Biorxiv : the Preprint Server for Biology
    |December 18, 2023
    PubMed
    Summary

    The subthalamic nucleus (STN) normally increases activity during locomotion, contrary to prior beliefs. This STN activity is crucial for proper movement speed and continuation.

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    Area of Science:

    • Neuroscience
    • Motor Control
    • Basal Ganglia Function

    Background:

    • The subthalamic nucleus (STN) is traditionally viewed as a movement inhibitor.
    • However, most STN neurons show increased firing during movement, creating a paradox.
    • This challenges the established role of the STN in motor control.

    Approach:

    • Recorded and manipulated STN neural activity in head-fixed mice during treadmill locomotion.
    • Utilized optogenetics to inhibit dorsolateral STN neurons.
    • Examined STN activity in Q175 Huntington's disease mouse model.

    Key Points:

    • The majority of STN neurons (type 1) increase activity during locomotion, with some encoding the locomotor cycle.
    • Optogenetic inhibition of dorsolateral STN neurons impaired locomotion, causing slowing and premature termination.
    • Hyperactivity of type 1 STN neurons correlated with abnormal locomotion in Huntington's disease mice.

    Conclusions:

    • Movement-related increases in STN activity are essential for optimal locomotor performance.
    • The STN's role in movement is more complex than previously understood, potentially facilitating rather than inhibiting movement.
    • Findings suggest a novel function of the STN in motor control and provide insights into movement disorders.