Modern Medical Laboratory Journal

Researchers in Salk Institute pinpoint a sound-sensitive mammalian protein that lets them activate brain, heart or other cells with ultrasound. The method, which the team used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps. The findings were published in Nature Communications on February 9, 2022.

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. In this study, They 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, they 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.
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