Targeted millisecond-scale activation of cells using non-invasive Sonogenetics

Duque, M.; Lee-Kubli, C.; Tufail, Y.; Magaram, U.; Lopez, J. M.; Edsinger, E.; Vasan, A.; Shiao, R.; Weiss, C.; Friend, J.; Chalasani, S. H.

doi:10.1101/2020.10.14.338699

bioRxiv · 10.1101/2020.10.14.338699

Targeted millisecond-scale activation of cells using non-invasive Sonogenetics

Duque, M.·Lee-Kubli, C.·Tufail, Y.·Magaram, U.·Lopez, J. M.·Edsinger, E.·Vasan, A.·Shiao, R.·Weiss, C.·Friend, J.·Chalasani, S. H.

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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.

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Duque, M., Lee-Kubli, C., Tufail, Y., Magaram, U., Lopez, J. M., Edsinger, E., Vasan, A., Shiao, R., Weiss, C., Friend, J., Chalasani, S. H.. 2020-10-15. Targeted millisecond-scale activation of cells using non-invasive Sonogenetics. https://doi.org/10.1101/2020.10.14.338699

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