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Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

Marc Duque, Corinne A. Lee-Kubli, Yusuf Tufail, Uri Magaram, Janki Patel, Ahana Chakraborty, Jose Mendoza Lopez, Eric Edsinger, Aditya Vasan, Rani Shiao, Connor Weiss, James Friend, Sreekanth H. Chalasani
doi: https://doi.org/10.1101/2020.10.14.338699
Marc Duque
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Corinne A. Lee-Kubli
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Yusuf Tufail
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Uri Magaram
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
2Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093
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Janki Patel
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Ahana Chakraborty
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Jose Mendoza Lopez
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Eric Edsinger
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Aditya Vasan
3Medically Advanced Devices Laboratory, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering and the Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA 92093
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Rani Shiao
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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Connor Weiss
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
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James Friend
3Medically Advanced Devices Laboratory, Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering and the Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA 92093
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Sreekanth H. Chalasani
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037
2Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093
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  • For correspondence: schalasani@salk.edu
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Abstract

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals1–4. However, this approach is limited as it has been challenging to target specific cells within the brain or body5–8. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show that hsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to c-fos expression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate that hsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 07, 2021.
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Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels
Marc Duque, Corinne A. Lee-Kubli, Yusuf Tufail, Uri Magaram, Janki Patel, Ahana Chakraborty, Jose Mendoza Lopez, Eric Edsinger, Aditya Vasan, Rani Shiao, Connor Weiss, James Friend, Sreekanth H. Chalasani
bioRxiv 2020.10.14.338699; doi: https://doi.org/10.1101/2020.10.14.338699
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Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels
Marc Duque, Corinne A. Lee-Kubli, Yusuf Tufail, Uri Magaram, Janki Patel, Ahana Chakraborty, Jose Mendoza Lopez, Eric Edsinger, Aditya Vasan, Rani Shiao, Connor Weiss, James Friend, Sreekanth H. Chalasani
bioRxiv 2020.10.14.338699; doi: https://doi.org/10.1101/2020.10.14.338699

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