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 and Sreekanth H. Chalasani ()
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Marc Duque: The Salk Institute for Biological Studies
Corinne A. Lee-Kubli: The Salk Institute for Biological Studies
Yusuf Tufail: The Salk Institute for Biological Studies
Uri Magaram: The Salk Institute for Biological Studies
Janki Patel: The Salk Institute for Biological Studies
Ahana Chakraborty: The Salk Institute for Biological Studies
Jose Mendoza Lopez: The Salk Institute for Biological Studies
Eric Edsinger: The Salk Institute for Biological Studies
Aditya Vasan: University of California San Diego
Rani Shiao: The Salk Institute for Biological Studies
Connor Weiss: The Salk Institute for Biological Studies
James Friend: University of California San Diego
Sreekanth H. Chalasani: The Salk Institute for Biological Studies

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals. However, this approach is limited as it has been challenging to target specific cells within the brain or body. 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28205-y

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DOI: 10.1038/s41467-022-28205-y

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