ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain

Abstract

CNS neurons have no sensory function, protected by the skull. For this reason, brain neuromodulation by ultrasound were either done at a high intensity or through auditory nerves. We demonstrate in this study CNS neurons react to ultrasound stimulation at an intensity (5 mW/cm2) far lower than typical therapeutic ultrasound (>30 mW/cm2). Using micropipette ultrasound in calcium imaging, we show ASIC1a channels play a role in the reactions of CNS neurons to ultrasound, pointing to the molecular basis for direct ultrasound neuromodulation at low intensity. Furthermore, we also show evidence of neurogenesis with the same ultrasound stimulation, suggesting potential therapeutic translation.

Data availability

All data generated relevant to this study are included in the manuscript are presented in the manuscript either as main figures or as supplementary figures. Source data files will be provided when there is a need.

Article and author information

Author details

  1. Jormay Lim

    Department of Biomedical Engineering, College of Medicine and College of Engineering,, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7191-545X
  2. Hsiao-Hsin Tai

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  3. Wei-Hao Liao

    Department of Rehabilitations, National Taiwan University Hospital, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  4. Ya-Cherng Chu

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  5. Chen-Ming Hao

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  6. Yueh-Chun Huang

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  7. Cheng-Han Lee

    Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  8. Shao-Shien Lin

    Department of Neurosurgery, National Taiwan University Hospital, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  9. Sherry Hsu

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  10. Ya-Chih Chien

    Academia Sinica, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  11. Dar-Ming Lai

    Department of Neurosurgery, National Taiwan University Hospital, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  12. Wen-Shiang Chen

    Department of Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  13. Chih-Cheng Chen

    Academia Sinica, Taipei, Taiwan
    For correspondence
    chih@ibms.sinica.edu.tw
    Competing interests
    The authors declare that no competing interests exist.
  14. Jaw-Lin Wang

    Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
    For correspondence
    jlwang@ntu.edu.tw
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5734-9276

Funding

Ministry of Science and Technology, Taiwan (MOST 107-2221-E-002-068-MY3)

  • Jaw-Lin Wang

Ministry of Science and Technology, Taiwan (MOST108-2321-B-002-047)

  • Jaw-Lin Wang

Ministry of Science and Technology, Taiwan (MOST 108-2321-B-002-061-MY2)

  • Jaw-Lin Wang

National Health Research Institutes (NHRI-EX109-10924EI)

  • Jaw-Lin Wang

Ministry of Science and Technology, Taiwan (MOST 108-2321-B-001-028-MY2)

  • Chih-Cheng Chen

Ministry of Science and Technology, Taiwan (MOST 110-2321-B001-010)

  • Chih-Cheng Chen

National Taiwan University (NTU-CC-107L891105)

  • Jaw-Lin Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animal work has been performed following the recommendations in the Guide for the Care and Use of Laboratory Animals of National Taiwan University. All of the animals handling complies to the IACUC protocol #20190055 of National Taiwan University Hospital.

Reviewing Editor

  1. Rohini Kuner, Universität Heidelberg, Germany

Version history

  1. Preprint posted: July 10, 2020 (view preprint)
  2. Received: July 31, 2020
  3. Accepted: September 22, 2021
  4. Accepted Manuscript published: September 27, 2021 (version 1)
  5. Version of Record published: October 12, 2021 (version 2)

Copyright

© 2021, Lim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jormay Lim
  2. Hsiao-Hsin Tai
  3. Wei-Hao Liao
  4. Ya-Cherng Chu
  5. Chen-Ming Hao
  6. Yueh-Chun Huang
  7. Cheng-Han Lee
  8. Shao-Shien Lin
  9. Sherry Hsu
  10. Ya-Chih Chien
  11. Dar-Ming Lai
  12. Wen-Shiang Chen
  13. Chih-Cheng Chen
  14. Jaw-Lin Wang
(2021)
ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain
eLife 10:e61660.
https://doi.org/10.7554/eLife.61660

Share this article

https://doi.org/10.7554/eLife.61660

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