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

Nat Commun. 2022 Feb 9;13(1):600. doi: 10.1038/s41467-022-28205-y.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Calcium / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / metabolism
  • TRPA1 Cation Channel / genetics*
  • TRPA1 Cation Channel / metabolism*
  • Transient Receptor Potential Channels / genetics*
  • Transient Receptor Potential Channels / metabolism*

Substances

  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Calcium