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

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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.

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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

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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.

"This ORCID iD identifies the author of this article:" 0000-0001-7191-545X
Hsiao-Hsin Tai

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

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The authors declare that no competing interests exist.
Wei-Hao Liao

Department of Rehabilitations, National Taiwan University Hospital, Taipei, Taiwan

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The authors declare that no competing interests exist.
Ya-Cherng Chu

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

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The authors declare that no competing interests exist.
Chen-Ming Hao

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

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The authors declare that no competing interests exist.
Yueh-Chun Huang

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

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The authors declare that no competing interests exist.
Cheng-Han Lee

Academia Sinica, Taipei, Taiwan

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The authors declare that no competing interests exist.
Shao-Shien Lin

Department of Neurosurgery, National Taiwan University Hospital, Taipei, Taiwan

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The authors declare that no competing interests exist.
Sherry Hsu

Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan

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The authors declare that no competing interests exist.
Ya-Chih Chien

Academia Sinica, Taipei, Taiwan

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The authors declare that no competing interests exist.
Dar-Ming Lai

Department of Neurosurgery, National Taiwan University Hospital, Taipei, Taiwan

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The authors declare that no competing interests exist.
Wen-Shiang Chen

Department of Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan

Competing interests
The authors declare that no competing interests exist.
Chih-Cheng Chen

Academia Sinica, Taipei, Taiwan

For correspondence
chih@ibms.sinica.edu.tw

Competing interests
The authors declare that no competing interests exist.
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.

"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.

Copyright

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.